No abstract available.
Azacitidine* ; Humans

No abstract available.
Azacitidine* ; Bandages* ; Myelodysplastic Syndromes*

No abstract available.
Anemia, Refractory* ; Azacitidine* ; Erythropoietin* ; Leukemia, Myelomonocytic, Chronic*

Azacitidine ; analogs & derivatives ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy

No abstract available.
Azacitidine ; Decitabine ; Leukemia, Myeloid, Acute ; Salvage Therapy ; Myelodysplastic Syndromes

OBJECTIVE: To study therapeutic efficacy and side effects of single decitabine for DNMT3A myelodysplastic syndrome (MDS) patients. METHODS: The clinical characteristics, efficacy and side effects of 59 myelodysplastic syndrome patients received the decitabine therapy in our center from January 2015 to December 2018 were retrospectively analyzed. Based on gene mutations, these patients were divided into 2 groups: DNMT3A MDS patients (n=27) and DNMT3A MDS patients (n=32). All patients in two groups were treated with decitabine for 4 circles. The efficacy and side effects in the two groups were compared. RESULTS: The median age of patients in DNMT3A MDS group was 56.2 (37-81) which was no statistic difference from DNMT3A MDS group. And there was no statistical difference including age, white blood cells, hemoglobin and platelet count between the two groups (P＞0.05). The ORR and complete response (CR) rate of DNMT3A group were 70.37% and 40.74%, the ORR and CR rate of DNMT3A group were 40.63% and 21.88% respectively. Significant differences were observed in ORR rate (P=0.035) between two groups. However, significant differences did not found in CR rate (P=0.159) between two groups, The similar adverse reaction was observed in DNMT3A and DNMT3A MDS patients. Among the 59 patients, 21 patients showed TP53+ mutation. DNMT3A/TP53 MDS patients (n=13) had similar ORR and CR compared with the DNMT3A/TP53 MDS patients (n=8) (P＞0.05). The overall survival (OS) in DNMT3A MDS group and DNMT3A MDS group were 29.1±13.4 months and 27.8±14.4 months, respectively, no significant differences between two groups were observed (P=0.475). CONCLUSION Decitabine treatment is an effective and safe for DNMT3A MDS patients, but not shows better survival advantage.
Azacitidine ; Decitabine ; Humans ; Myelodysplastic Syndromes ; Retrospective Studies ; Treatment Outcome

BACKGROUND: Azacitidine (AZA) is standard care for patients with myelodysplastic syndrome (MDS) who have not had allogeneic stem cell transplantation. Chromosomal abnormalities (CA) including complex karyotype (CK) or monosomal karyotype (MK) are associated with clinical outcome in patients with MDS. METHODS: We investigated which prognostic factors including CAs would predict clinical outcomes in patients with International Prognostic Scoring System (IPSS) higher risk MDS treated with AZA, retrospectively. CK was defined as the presence of three or more numerical or structural CAs. MK was defined as the presence of two or more distinct autosomal monosomies or single autosomal monosomy with at least one additional structural CA. RESULTS: A total of 243 patients who treated with AZA, were enrolled. CK was present in 124 patients and MK was present in 90 patients. Bone marrow blasts > or =15% and CK were associated with poorer response (P=0.038, P=0.007) and overall survival (OS) (P<0.001, P<0.001) independently. Although MK in CK group was not associated with prognosis, non-MK status in non-CK group reflected favorable OS (P=0.005). The group including >3 CAs was associated with poorer OS (group including <3 CAs vs. only three CAs, P=0.001; group with >3 CAs vs. only three CAs, P=0.001). CONCLUSION: CK was an important prognostic parameter associated with worse outcome. MK may predict poor survival in only non-CK status. The higher number of CAs was associated with poorer survival.
Azacitidine* ; Bone Marrow ; Chromosome Aberrations ; Humans ; Karyotype* ; Monosomy ; Myelodysplastic Syndromes* ; Prognosis ; Retrospective Studies ; Stem Cell Transplantation

Myelodysplastic syndrome (MDS) is a clonal marrow stem cell disorder, characterized by ineffective haemopoiesis leading to blood cytopenias. As a disease of grey zone, along with the development of research, the exploration on its pathogenesis have been shifted from molecular genetics and the feature of immunophenotype to the epigenetic and micro environment. But at present, the pathogenesis of MDS is still not clear, the research of the molecular genetics and immunophenotype can not meet the needs of experimental and clinical application any longer. The hematopoietic stem cells, cytokines, epigenetic studies, however, have made a lot of achievements. Targeted medicine such as azacitidine and decitabine had promising response in treating MDS patients. In this article the abnormality of stromal cells, cytokines and epigenetic changes in hematopoietic microenvironment of MDS are reviewed in order to optimize the monitoring MDS progress and guide its clinical medication strategy.
Azacitidine ; analogs & derivatives ; Bone Marrow ; Cytokines ; Hematopoietic Stem Cells ; Humans ; Immunophenotyping ; Myelodysplastic Syndromes ; Stromal Cells

BACKGROUND: Mesenchymal stromal cells (MSCs) are useful for cell therapy because of their potential for multilineage differentiation. However, MSCs that are expanded in traditional two-dimensional (2D) culture systems eventually lose their differentiation abilities. Therefore, we investigated whether azacitidine (AZA) supplementation and three-dimensional culture (3D) could improve the differentiation properties of MSCs. METHODS: 2D- or 3D-cultured MSCs which were prepared according to the conventional or hanging-drop culture method respectively, were treated with or without AZA (1 µM for 72 h), and their osteogenic and adipogenic differentiation potential were determined and compared. RESULTS: AZA treatment did not affect the cell apoptosis or viability in both 2D- and 3D-cultured MSCs. However, compared to conventionally cultured 2D-MSCs, AZA-treated 2D-MSCs showed marginally increased differentiation abilities. In contrast, 3D-MSCs showed significantly increased osteogenic and adipogenic differentiation ability. When 3D culture was performed in the presence of AZA, the osteogenic differentiation ability was further increased, whereas adipogenic differentiation was not affected. CONCLUSION: 3D culture efficiently promoted the multilineage differentiation of MSCs, and in combination with AZA, it could help MSCs to acquire greater osteogenic differentiation ability. This optimized culture method can enhance the therapeutic potential of MSCs.
Adipogenesis ; Apoptosis ; Azacitidine* ; Cell- and Tissue-Based Therapy ; Mesenchymal Stromal Cells* ; Methods ; Osteogenesis

OBJECTIVE: To investigate the changesof DNA methylation in histone deacetylases 4 gene (HDAC4) and its effectduring the trans-differentiation process of human mesenchymal stem cells (hMSCs) into sweat gland like cells (SGLCs). METHODS: Selected cell lines of human mesenchymal stem cells (hMSCs) were cultured and expended , the third generation ofhMSCs and heat-shocked sweat gland cells were picked up, and were co-culturedwith adding inducible factor in the transwell chamber. The sweat gland like cells (SGLCs)in experiment group and the hMSCs in control group were collected, the changes of DNA methylation degree of CpG dinucleotide sitesin histone deacetylases 4 gene (HDAC4) promotor were detected by methylation specific PCR (MSP)andMaldi-TOF Mass Array. And then, the hMSCs in experiment group were treated with 5-aza-CdR (5-aza-2-deoxycytidine, 10 μmol/L), while the hMSCsin control group were culturedwith PBS at the same time. ThemRNA expressions of HDAC4 gene and carcino-embryonic antigen (CEA)gene in the two groups were measured by RT-PCR. RESULTS: The methylation of HDAC4gene in hMSCs was in high level before induction, the methylation degreeof CpG dinucleotide sites located in cg2463009 was 0.901, and the methylation degree of HDAC4gene in SGLCs was markedly decreased by 37% after induction, which was 0.531. The methylationlevel of CpG dinucleotide sites located in cg14823429was changed from 0.687to 0.386 after induction. The mRNA expression of HDAC4 gene was upregulated in test group after treated with 5-aza-CdR for 48 hours, the mRNA expression of CEA gene related with transdifferentiation was enhanced too at the same term, there was significantly statistic difference compared with control group (<0.05). CONCLUSIONS Methylation of HDAC4 gene participates in the regulation of the trans-differentiation of hMSCs into sweet gland like cells.
Azacitidine ; Cell Differentiation ; DNA Methylation ; Histone Deacetylases ; Humans ; Mesenchymal Stem Cells ; Repressor Proteins ; Sweat Glands