hGCN5在Burkkit淋巴瘤细胞株Daudi中的表达及TSA对细胞增殖凋亡的影响

目的:研究hGCN5(human general control of amino acid synthesis protein 5)在Burkkit淋巴瘤细胞株Daudi中的表达及曲古柳菌素A(TSA)对细胞增殖、凋亡的影响,探讨其抗肿瘤的分子机制.方法:采用MTT法检测细胞增殖,流式细胞仪检测细胞周期和凋亡率,采用免疫细胞化学法和Western blot观察Daudi细胞hGCN5蛋白的表达.结果:TSA可明显抑制Daudi细胞增殖;TSA(50、100μg/L)使细胞积聚于G0/G1期;TSA(200μg/L)则使细胞周期受抑于S期,而对G2/M期的作用不明显;TSA(200、400μg/L)处理24h可以诱导细胞凋亡;免疫细胞化学和Westernblot结果均显示处理组hGCN5的吸光度比未处理组明显增加(P＜0.05).结论:TSA通过上调HATs家族成员中hGCN5的表达,实现对Daudi细胞的抗增殖作用.     

Effects of FK228, a novel histone deacetylase inhibitor,on human lymphoma U-937 cells in vitro and in vivo

FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo-[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone; FR901228, depsipeptide] is a novel histone deacetylase inhibitor that shows therapeutic efficacy in Phase I trials of patients with malignant lymphoma. However, its mechanism of action has not been characterized. In this study, we examined the in vitro and in vivo effects of FK228 on human lymphoma U-937 cells. FK228 very strongly inhibited the growth of U-937 cells with an IC(50) value of 5.92 nM. In a scid mouse lymphoma model, mice treated with FK228 once or twice a week survived longer than control mice, with median survival times of 30.5 (0.56 mg/kg) and 33 days (0.32 mg/kg), respectively (vs. 20 days in control mice). Remarkably, 2 out of 12 mice treated with FK228 (0.56 mg/kg once or twice a week) survived past the observation period of 60 days. The apoptotic population of U-937 cells time-dependently increased to 37.7% after 48 hr of treatment with FK228. In addition, FK228 induced G1 and G2/M arrest and the differentiation of U-937 cells to the CD11b(+)/CD14(+) phenotype. Expression of p21(WAF1/Cip1) and gelsolin mRNA increased up to 654- and 152-fold, respectively, after 24hr of treatment with FK228. FK228 caused histone acetylation in p21(WAF1/Cip1) promoter regions, including the Sp1-binding sites. In conclusion, (i) FK228 prolonged the survival time of scid mice in a lymphoma model, and (ii) the beneficial effects of FK228 on human lymphoma may be exerted through the induction of apoptosis, cell cycle arrest, and differentiation via the modulation of gene expression by histone acetylation.     

唾液酸作为肺癌标志物的ROC分析

用受试者试验特征性曲线（ROC）建立了血清TSA与LSA对肺癌与非癌患者的最佳诊断分界值（Cut－off），TSA为76mg／dl，LSA为23mg／dl，肺癌组TSA与LSA的含量均明显高林非癌组，同时比较了TSA与LSA的诊断灵敏度，特异性，符合率，ROCAUC和信息量。血清唾液酸作为肺癌标志物时，TSA与LSA的ROCAUC无显著性差异（P＞O．05），二者间信息量的u值为0．91，P＞0．05。提示只要选一个最佳cut－off值，单测血清TSA就有可能达到筛选肺癌的目的。     

颅内肿瘤患者血清总唾液酸测定的临床意义

作者对正常健康人73名、颅内良性肿瘤40例、恶性胶质瘤30例及脑转移瘤13例的血清TSA进行测定。结果显示：所有颅内肿瘤患者组血清TSA水平均显著高于正常对照组，其中，脑转移瘤组最高，恶性胶质瘤组次之，良性肿瘤组居第三位。所以，测定血清TSA水平对CT或MRL显示的颅内肿瘤的性质判定具有辅助诊断价值。     

胸水CA50、唾液酸、癌胚抗原、铁蛋白及白介素—8检测对鉴别良、恶性胸水的价值

目的：评价胸水糖链抗原50（CA50）、唾液酸（TSA）、癌胚抗原（CEA）、铁蛋白（SF）及白介素－8（IL－8）对鉴别良、恶性胸水的价值。方法：结核性胸膜炎组（A组）患者40例,恶性胸水组（B组）34例,均经临床及病理证实。采用放免法测定胸水CEA、CA50、SF;采用Joudian氏法测定胸水TSA;采用酶联免疫双抗体夹心法检测胸水IL－8,比较A、B两组胸水测定值差异及各项测定的灵敏度、特异性及五项联检、CEA＋CA50检测的灵敏度及特异性。结果：B组五项检测值均与A组存在显著差异（P＜0．01及0．001）,五项联检灵敏度提高到88％,与单项检测相比差异显著（P＜0．05）,特异性77％,较CA50＋CEA显著降低（P＜0．05）。CEA＋CA50联检特异性为95％,灵敏度为79％,较CA50、TSA、CEA、SF、IL－8、CEA单项检查增高（P＜0．05）。结论：胸水CA50、TSA、CEA、SF及IL－8测定对鉴别良、恶性胸水有重要意义,上述五项联检可有效降低恶性胸水漏诊率,胸水CA50＋CEA联检可作为筛选恶性胸水有价值的指标。     

Epigenetic regulation in the pathophysiology of Alzheimer's disease

With the aging of the population, the growing incidence and prevalence of Alzheimer's disease (AD) increases the burden on individuals and society as a whole. To date, the pathophysiology of AD is not yet fully understood. Recent studies have suggested that epigenetic mechanisms may play a pivotal role in its course and development. The most frequently studied epigenetic mechanisms are DNA methylation and histone modifications, and investigations relevant to aging and AD are presented in this review. Various studies on human postmortem brain samples and peripheral leukocytes, as well as transgenic animal models and cell culture studies relevant to AD will be discussed.     

萆薢总皂苷合用牛膝总皂苷降血尿酸和抗炎作用的组方合理性研究

目的探讨牛膝总皂苷和萆薢总皂苷降低小鼠血尿酸和抗炎作用的组方合理性及剂量配比。方法采用尿酸或酵母膏致小鼠高尿酸血症模型以及二甲苯致小鼠耳肿胀模型,按照Codrug软件,得优化组方。结果萆薢总皂苷组、牛膝总皂苷+萆薢总皂苷组和阳性对照组小鼠血清尿酸水平明显降低(P<0.01),牛膝总皂苷480、240、120mg.kg-1组小鼠血清尿酸水平与模型组比较差异无显著性。牛膝总皂苷、萆薢总皂苷对小鼠耳肿胀均有明显的抑制作用,两者合用抑制率强于单药组,两药配伍理论优化剂量为牛膝总皂苷为120mg.kg-1,萆薢总皂苷为240mg.kg-1。结论萆薢总皂苷能降低高尿酸血症小鼠血清尿酸水平,而牛膝总皂苷对小鼠血清尿酸水平无明显影响。两者均有较强的抗炎作用,合用抗炎作用增强,优化组方为牛膝总皂苷∶萆薢总皂苷=1∶2。     

曲古菌素A对HeLa细胞增殖及其基因表达的影响研究

Objective:To investigate the expressions of p53,RB1,Fas,c-fos,Ras,EGFR mRNA in human cervical cancer (HeLa) cell in response to the trichostatin A (TSA).Methods:We took count of HeLa cells in different incubation times with TSA (0.2 IJm/L).The result indicated that HeLa cells changed evidently when HeLa cells were incubated for 36 h.Then,we investigated the genes expression (mRNA levels) of HeLa cells after treatment for 36 h using SYBR green real-time PCR.Results:We demonstrated that trichostatin A (TSA) could make human cervical cancer (HeLa) cell morphological change and induce HeLa cell apoptosis.Furthermore,the data suggest that TSA-induced down-regulation of p53,RB1,Fas,but upregulated c-fos gene expression after treatment for 36 h,and Ras,EGFR did not show obvious response to TSA treatments.Conclusion:TSA has different effects on gene expression.     

MicroRNA miR-182 cluster mediated modulation of RECK without changes in cell surface membrane type-1 matrix metalloproteinase (MT1-MMP)

Cell surface localized membrane type 1-matrix metalloproteinase (MT1-MMP) plays an important role in physiological and pathological processes and its function can be regulated by proteins such as RECK. We examined the ability of miR-182 (one of the miR-183 cluster miRNAs), which can target RECK, to control cell surface MT1-MMP activity. Expression of RECK mRNA and protein was increased with anti-miRs to miR-182, miR-183 or miR-96 in HT1080 fibrosarcoma cells, but, decreased RECK mRNA and increased its protein in the benign prostatic hyperplasia cell line BPH-1. Treatment of BPH-1 and HT-1080 cells with the anti-miRs did not change the level of cell surface MT1-MMP activity, nor their rate of migration in an in vitro wound-healing assay. Trichostatin A (TSA) did not increase the level of RECK, but blocked cell surface MT1-MMP activity and decreased cell motility. Anti-miRs mediated increased RECK levels did not interfere with cell surface MT1-MMP function, and TSA may block cell surface localization of MT1-MMP by a mechanism independent of RECK.