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<p><b>OBJECTIVE</b>To investigate the expression level and regulation mechanism of miR-720 as well as the association of miR-720 expression with leukemia biological characteristics.</p><p><b>METHODS</b>Expression and promoter methylation of miR-720 were determined by quantitive PCR and pyrosequencing in 38 patients with AML and 20 normal controls. Lentivirous-mediated miR-702 overexpression was constructed in AML cell line kasumi-1. The cell proliferation, apoptosis, cycle, colony formation, migration and P53-mediated apoptosis pathway were determined.</p><p><b>RESULTS</b>AML patients showed significantly lower miR-720 expression compared with normal controls (0.69±0.09 vs 3.00±0.46, P<0.01); The methylation level of miR-720 promoter region in AML patients were significantly higher than normal controls [(75.56±2.35)% vs (47.65±2.78)%, P<0.01]. miR-720 overexpression in kasumi-1 cells induced significantly increased cell apoptosis (P=0.017), elevated apoptosis sensitivity to etoposide (P=0.004), and reduced cell proliferation (P<0.01). miR-720 overexpression also induced reduced colony formation (P=0.005), cell cycle arrest in G(1)/G(0) phase and decreased migration ability in kasumi-1 cells. In addition, overexpression of miR-720 significantly induced increased cell apoptosis-related proteins including P53 and Bax, and activation of NF-κB signal transduction pathway. After kasumi-1 cells were treated with 1uM decitabine for 48 hours, miR-720 promoter methylation reduced significantly, and miR-720 expression significantly increased.</p><p><b>CONCLUSION</b>The expression of miR-720 in AML patients reduced significantly, and DNA methylation-mediated epigenetic silencing of miR-720 contributed to maintain the malignant characteristics of AML.</p>
Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , DNA Methylation , Epigenesis, Genetic , Leukemia, Myeloid, Acute , Genetics , Pathology , MicroRNAs , Genetics , Promoter Regions, GeneticABSTRACT
To study the therapeutic effects of low-dose amiodarone and Betaloc on hypertrophic cardiomyopathy complicated by malignant ventricular arrhythmias. Eighty-two such patients were selected and divided into a treatment group and a control group by the random number method [n=41], which were administered with low-dose amiodarone plus Betaloc and individual Betaloc respectively. The treatment group had a significantly higher overall effective rate [85.4%] than the control group [65.9%] did. Based on the New York Heart Association's classification of cardiovascular disease, the treatment group mainly comprised Class III and IV patients before treatment, which were significantly relieved after treatment [P < 0.05]. The heart rate was evidently decreased from [119.99 +/- 18.91] bpm to [80.98 +/- 12.34] bpm, and the incidences of premature ventricular contraction and tachycardia were significantly reduced [P < 0.05]. The longest QT intervals after and before treatment were [421 +/- 32] ms and [411 +/- 35] ms respectively. The shortest QT interval after treatment [[350 +/- 36] ms] was significantly longer than that before [[307 +/- 31] ms]. The QT dispersion before treatment [[96 +/- 29] ms] was significantly higher that after [[64 +/- 17] ms] [P < 0.05]. Six out of eighty two patients in the treatment group succumbed to adverse reactions [14.63%]. Hypertrophic cardiomyopathy complicated with malignant ventricular arrhythmias can be well treated with low-dose amiodarone and Betaloc, with mitigated symptoms, improved prognosis and few adverse reactions
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Objective To investigate the effect of atorvastatin on vascular endothelial cell function and vasoactive substances in essential hypertensive patients without hyperlipemia. Methods Sixty-five essential hypertensive(EH) patients without hyperlipemia were enrolled and randomly divided into atorvastatin group and conventional treatment group(oral taken atorvastatin or placebo once every night in addition of routine antihypertensive drugs).Twenty five healthy subjects were also recruited as control.All cases were followed up for eight weeks.Serum cholesterol,nitric oxide(NO),emdothelin-1(ET-1),vonWillebrand-factor(vWF) levels were determined in each case.Flow-medizted dilation(FMD) was determined by high-resolution ultrasonography before and after eight weeks atorvastatin medication.Results (1)Before treatment,the FMD and NO levels of EH group were significantly lower than those of control group(P＜0.01),while the ET-1 and vWF levels of EH group were significantly higher than those of control group(P＜0.01);(2)In EH patients,the FMD and NO levels significantly increased after treatment and increased even more dramatically in atorvastatin group,when compared to conventional treatment group(Ps＜0.01);(3)In EH patients,the ET-1 and vWF levels significantly decreased after treatment and decreased even more dramatically in atorvastatin group,when compared to conventional treatment group(Ps＜0.01).Conclusion In patients of EH without hyperlipemia,atorvastatin can decrease plasma levels of ET-1,vWF,while increase plasma NO concentration and improve vascular endothelial function.
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Objective To determine the results of treatment combining all-trans-retinoic acid(ATRA)in childhood acute promyelocytic leukemia(APL).Methods 22 children with newly diagnosed APL received induction therapy with ATRA followed by 3 courses of consolidation chemotherapy:daunorubicin,idarubicin,homoharringtonine or aclacinomycin plus cytosine arabinoside.A maintenance therapy was then administered with ATRA and these reigems for 36 months.Results Early deaths from diffuse intravazcular clotting and intracranial hemorrhage occurred in two patients.The other children achieved a complete remission(CR).By June 2007,the estimated disease-free survival rates at 1,3 and 5 years were 100%,93.3% and 84.7%;respectively.The side effects of ATRA were xerosis eutis and xerocheilia,headaches,nausea and vomiting,hepatic function lesion and ATRA syndrome.Conclusion Remission induction therapy with ATRA is effective and safe for newly diagnosed childhood APL.The maintenance therapy combined chemotherapy with ATRA can improve the long-term effects of APL patients.The main causes of death in APL children is diffuse intravascular clotting and intracranial hemorrhage.The side effects of ATRA can be tolerated.
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<p><b>OBJECTIVE</b>To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte beta-adrenoceptors (beta-ARs) of patients with chronic congestive heart failure (CHF).</p><p><b>METHODS</b>Twenty-eight patients with class III or IV advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T(50)) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and (125)I-pindolol radioligand binding was used to measure beta-AR levels in peripheral lymphocytes.</p><p><b>RESULTS</b>L-T(50) therapy improved cardiac output [CO, (2.98 +/- 0.31)L/min vs (3.24 +/- 0.28) L/min, P < 0.01], left ventricular ejection fraction (LVEF, 26.21% +/- 3.21% vs 37.93% +/- 9.01%, P < 0.01), and decreased isovolumetric relaxation time (IVRT, 0.12 +/- 0.04 vs 0.10 +/- 0.02, P < 0.01). Serum TH levels and the maximal number of beta-AR binding sites (beta(max)) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T(50) administration induced a beta-AR up-regulation on peripheral lymphocyte surfaces. L-T(50) was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.</p><p><b>CONCLUSION</b>TH administration improves cardiac function and beta-AR expression in peripheral lymphocytes of patients with CHF.</p>