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In order to investigate the expression and functional role of HERG1 K channels in leukemic cells and leukemic stem cells (LSCs), RT-PCR was used to detect the HERG1 K channels expression in leukemic cells and LSCs. The functional role of HERG1 K channels in leukemic cell proliferation was measured by MTT assay, and cell cycle and apoptosis were analyzed by flow cy- tometry. The results showed that herg mRNA was expressed in CD34 /CD38-, CD123 LSCs but not in circulating CD34 cells. Herg mRNA was also up-regulated in leukemia cell lines K562 and HL60 as well as almost all the primary leukemic cells while not in normal peripheral blood mononuclear cells (PBMNCs) and the expression of herg mRNA was not associated with the clinical and cytoge- netic features of leukemia. In addition, leukemic cell proliferation was dramatically inhibited by HERG K channel special inhibitor E-4031. Moreover, E-4031 suppressed the cell growth by induc- ing a specific block at the G1/S transition phase of the cell cycle but had no effect on apoptosis in leukemic cells. The results suggested that HERG1 K channels could regulate leukemic cells prolif- eration and were necessary for leukemic cells to proceed with the cell cycle. HERG1 K channels may also have oncogenic potential and may be a biomarker for diagnosis of leukemia and a novel potential pharmacological target for leukemia therapy. 相似文献
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目的研究组蛋白去乙酰化酶抑制剂曲古菌素A(trichostatin A, TSA)抑制HL-60细胞端粒酶活性及亚单位hTERT的表达并诱导凋亡的机制。方法采用MTT法和倒置相差显微镜观察不同浓度曲古菌素A对HL-60细胞的抑制作用,流式细胞仪检测600 nmol·L-1TSA作用后的细胞凋亡情况,TRAP-ELISA法检测端粒酶活性变化,RT-PCR分析端粒酶三个亚单位的mRNA表达情况。结果 TSA对HL-60细胞的抑制作用具有时间和剂量依赖性,AnnexinV/PI双染色法检测凋亡显示,600 nmol·L-1TSA作用48 h后,细胞凋亡率为42·6%。600 nmol·L-1TSA作用12、24和48 h后,端粒酶活性分别下降到1·95 ±0·25、1·73 ±0·12和1·52 ±0·09。RT-PCR显示,端粒酶逆转录酶hTERT表达下降,而端粒酶RNA模板(hTR)和端粒酶相关蛋白(hTP1)表达无明显改变。结论 TSA抑制HL-60细胞中端粒酶活性,并诱导凋亡,其机制可能与曲古菌素A下调hTERT转录水平有关。 相似文献
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皮下脂肪和胎盘的抵抗素表达及与胰岛素抵抗的关系 总被引:2,自引:0,他引:2
目的探讨抵抗素与胰岛素抵抗(IR)、肥胖和糖尿病的关系。方法于2003-032004-12选取武汉协和医院正常人腹部(n=12)、腿部(n=8)、妊娠妇女腹部(n=12)皮下脂肪组织和胎盘(n=12)为标本,以Western blot法检测抵抗素蛋白表达情况,测定血糖、血脂、胰岛素、体重、身高,计算IR指数、体重指数(BMI)、体内脂肪百分比(BF%)。结果妊娠妇女胎盘组抵抗素蛋白(67905±8441)(OD值)的表达明显高于妊娠腹部组(40718±3818)(P<0·01);正常人腹部组(39421±6087)(P<0·01)、腿部组皮下脂肪组织(14942±6706)(P<0·001);妊娠腹部组和正常人腹部组皮下脂肪组织均明显高于腿部组(P<0·001);抵抗素蛋白与BMI、IR指数、BF、空腹血糖呈正相关性。结论胎盘可分泌抵抗素,抵抗素与中心性肥胖有密切关系,可能引起IR,导致肥胖、2型糖尿病和妊娠糖尿病。 相似文献
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[摘要]目的: 构建痘苗生长因子(vaccinia growth factor,VGF)和胸苷激酶(thymidine kinase,TK)双基因缺失同时表达绿色荧光蛋白(GFP)和DsRed双荧光的溶瘤痘病毒,并研究其对胰腺癌细胞的杀伤作用。方法: 在病毒TK基因处利用同源重组方法将病毒晚期启动子F17R调控的GFP基因和早晚期启动子SEL调控的DsRed基因克隆入缺失VGF基因的VSC20亲本病毒,构建同时缺失VGF和TK双基因的重组溶瘤痘病毒vvDD-GFP DsRed。同时利用CCK 8法和结晶紫染色法检测该病毒对胰腺癌细胞Patu8988和BxPC-3的杀伤作用。结果: 通过同源重组和软琼脂筛选获得vvDD-GFP-DsRed重组溶瘤痘病毒。CCK 8法结果显示,与MOI=0相比,MOI分别为1,10时,vvDD-GFP-DsRed对Patu8988细胞和BxPC-3细胞具有明显的杀伤作用,且在此范围内随MOI值增加杀伤效果逐渐增强(P均<0.05)。与MOI=0相比,Patu8988细胞在MOI为0.01时存活率低(P<0.05),且在结晶紫染色法测定中形成了明显的空斑。结论: 成功构建vvDD GFP DsRed重组溶瘤痘病毒,其对胰腺癌细胞具有明显的杀伤作用。 相似文献
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目的:探讨再生障碍性贫血( AA)患者外周血NK细胞及CIK细胞与疗效的关系。方法应用流式细胞仪检测51例AA患者[急性AA( AAA)30例,慢性AA( CAA)21例]治疗前后与40例健康对照组NK细胞、CIK细胞的表达。结果(1) AA患者外周血CD4+、CD4+/CD8+、NK细胞的比例显著低于对照组( P<0.05), CD8+、CIK细胞的比例显著高于对照组(P<0.05),AAA组与CAA组之间的差异有统计学意义(P<0.05)。(2)疗效好的患者NK细胞比值升高,CIK细胞比值无明显下降。结论 AA患者存在多种免疫异常,多种因素参与AA的发病机制。检测免疫细胞将有助于评估AA的病情及疗效。 相似文献
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Summary In order to investigate the expression and functional role of HERG1 K+ channels in leukemic cells and leukemic stem cells (LSCs), RT-PCR was used to detect the HERG1 K− channels expression in leukemic cells and LSCs. The functional role of HERG1 K+ channels in leukemic cell proliferation was measured by MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry.
The results showed that herg mRNA was expressed in CD34+/CD38−, CD123− LSCs but not in circulating CD34+ cells. Herg mRNA was also up-regulated in leukemia cell lines K562 and HL60 as well as almost all the primary leukemic cells
while not in normal peripheral blood mononuclear cells (PBMNCs) and the expression of herg mRNA was not associated with the
clinical and cytogenetic features of leukemia. In addition, leukemic cell proliferation was dramatically inhibited by HERG
K+ channel special inhibitor E-4031. Moreover, E-4031 suppressed the cell growth by inducing a specific block at the G1/S transition
phase of the cell cycle but had no effect on apoptosis in leukemic cells. The results suggested that HERG1 K+ channels could regulate leukemic cells proliferation and were necessary for leukemic cells to proceed with the cell cycle.
HERG1 K+ channels may also have oncogenic potential and may be a biomarker for diagnosis of leukemia and a novel potential pharmacological
target for leukemia therapy.
LI Huiyu, female, born in 1960, Associate Professor
This project was supported by a grant from National Science Foundation for Distinguished Young Scholars of China (No. 30225038). 相似文献
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herg1(human ether-a-go-go-related gene) 基因是电压门控钾离子通道成员,其编码的HERG1钾通道选择性表达于多种组织来源的肿瘤细胞系及原代肿瘤细胞,调节肿瘤细胞增殖、分化、凋亡,与肿瘤的侵袭力和化疗敏感性密切相关。这为肿瘤的诊断、预后评估和肿瘤靶向治疗提供了一个新的特异性分子标志。 相似文献
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目的:探讨毛囊黏蛋白病的临床表现、分型及病理特征。方法:应用常规病理方法观察1例毛囊黏蛋白病,并进行相关文献复习。结果:患者以全身多发皮下结节为临床表现,病理示表皮未见明显异常,皮乳头层下毛囊、皮脂腺、汗腺、血管周围、胶原间见淡灰蓝色黏蛋白沉积,血管周围少量淋巴组织细胞浸润、阿新蓝染色(pH2.5)强阳性。皮疹出现6个月后患者出现全身淋巴结肿大并血常规异常,骨髓涂片、骨髓免疫分型及淋巴结活检诊断急性单核细胞白血病。诊断符合毛囊黏蛋白病并发急性单核细胞白血病。结论:毛囊黏蛋白病是临床少见病,具有特殊病理特点,并发急性单核细胞白血病更是罕见,国内目前未见相关报道。 相似文献