ABSTRACT
This study was aimed to investigate the effect of valproic acid (VPA), a histone deacetylase inhibitor, on angiogenesis of acute myeloid leukemia in vivo and vitro, and to explore its molecular mechanism. Human t (8;21) AML cell line Kasumi-1 cells were treated with VPA at different concentration for 3 d, the mRNA and protein expression levels of Ang1 and Ang2 were determined by semi-quantitative RT-PCR and Western blot respectively. Nude mice model with xenograft Kasumi-1 tumor was established by subcutaneous inoculation of Kasumi-1 cells. The CD34, Ang1 and Ang2 protein levels were analyzed by immunohistochemistry method. The mRNA and protein expression levels of Ang1, Ang2 and VEGF were determined by semi-quantitative RT-PCR and Western blot. The results showed that in vitro, VPA at 3 mmol/L downregulated the Ang mRNA relative expression level for Ang1 from 0.360 ± 0.116 to 0.040 ± 0.008, Ang2 from 0.540 ± 0.049 to 0.146 ± 0.038. The animal experiment further verified that VPA 500 mg/kg, ip, for 14 d, reduced the relative expression of Ang1, Ang2 and VEGF mRNA and proteins in Kasumi-1 tumor of nude mice, and reduced microvascular density in xenograft tumor of nude mice (8.470 ± 0.300 vs 2.600 ± 0.200). It is concluded that VPA significantly inhibits tumor angiogenesis through the regulation of angiopoietins, thereby inhibits the proliferation and metastasis of leukemia cells.
Subject(s)
Leukemia, Myeloid, Acute/pathology , Neovascularization, Pathologic , Valproic Acid/pharmacology , Angiopoietins/metabolism , Animals , Antigens, CD34/metabolism , Cell Line, Tumor , Female , Humans , Leukemia, Myeloid, Acute/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Neovascularization, Pathologic/metabolism , RNA, Messenger/genetics , Vascular Endothelial Growth Factor A/metabolism , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: To investigate the prevalence of sleep apnea-hypopnea syndrome (SAHS) among adults aged over 30 yr in Chengde city of Hebei province. METHODS: 1 168 subjects (over 30 yr) were derived from a random sample of the population among the Shuangqiao district in Chengde city. All subjects were asked at home to answer questions about their snoring, daytime sleepiness, and habits of smoking and drinking. According to the degree of snoring, 127 moderate and severe snorers were measured by portable PSG for a whole night and the prevalence of SAHS was estimated according to AHI and ESS scores. RESULTS: 1 168 subjects (95.42%) answered the questions. The prevalence of snoring was 53.76%. The prevalence of moderate and severe snoring (>or= second degree) was 28.25%. The prevalence of snoring increased with age before the age of 70. The prevalence of snoring in males was significantly higher than that in females. Smoking and drinking groups were associated with a higher prevalence of snoring. The prevalence of snoring was higher in drivers (42.00%) than that in other populations. The estimated prevalence of SAHS according to both the AHI > 5 and the ESS >or= 9 was 4.63%. CONCLUSIONS: The estimated prevalence of SAHS among adults aged over 30 yr in Chengde city was 4.63%. It means that SAHS needs better understanding and more study.
