慢性粒细胞性白血病不同病期bcr-abl基因 P53基因突变研究

探讨 bcr- abl融合基因、P53 基因对 CML不同病期演变的作用 .采取 CML2 6例不同分期共30份标本 ,应用逆转录—聚合酶链反应 (RT- PCR)技术检测 bcr- abl融合基因 ,应用多聚酶变 .结果显示 2 4例 CML慢性期中 2 2例 bcr- abl基因 ( ) ,6例急变期中 5例 bcr- abl基因 ( ) ;CML慢性期未发现 P53 基因突变 (0 / 2 4 ) ,急变期发现 2例突变 (2 / 6 ) .2例 P53 基因突变中 ,1例 bcr- abl基因( ) ,1例 bcr- abl基因 (- ) .由此可得 P53 基因突变在 CML慢性期少见 ;P53 基因突变对部分 CML急变有一定作用     

Unscheduled CDK1 activity in G1 phase of the cell cycle triggers apoptosis in X-irradiated lymphocytic leukemia cells

Cyclin-dependent kinase 1 (CDK1) is a major component of the cell cycle progression engine. Recently, several investigations provided evidence demonstrating that unscheduled CDK1 activation may also be involved in apoptosis in cancerous cells. In this article, we demonstrate that X-ray irradiation induced G1 arrest in MOLT-4 lymphocytic leukemia cells, the arrest being accompanied by reduction in the activity of CDK2, but increased CDK1 activity and cell apoptosis in the G1 phase. Interestingly, this increase in CDK1 and apoptosis by ionizing radiation was prevented by pretreatment with the CDK1 inhibitor, roscovitine, suggesting that CDK1 kinase activity is required for radiation-induced apoptotic cell death in this model system. Furthermore, cyclin B1 and CDK1 were detected co-localizing and associating in G1 phase MOLT-4 cells, with the cellular lysates from these cells revealing a genotoxic stress-induced increase in CDK1 phosphorylation (Thr-161) and dephosphorylation (Tyr-15), as analyzed by postsorting immunoprecipitation and immunoblotting. Finally, X-irradiation was found to increase Bcl-2 phosphorylation in G1 phase cells. Taken together, these novel findings suggest that CDK1 is activated by unscheduled accumulation of cyclin B1 in G1 phase cells exposed to X-ray, and that CDK1 activation, at the wrong time and in the wrong phase, may directly or indirectly trigger a Bcl-2-dependent signaling pathway leading to apoptotic cell death in MOLT-4 cells. Received 30 March 2006; received after revision 23 June 2006; accepted 24 August 2006 J. Wu and Y. Feng contributed equally to this work.     

Effects of mistletoe (Viscum album L.) extracts on cultured tumor cells

Summary Bacterially fermented mistletoe preparations (BFMP) were tested on rat hepatoma tissue culture (HTC) cells and human leukemia Molt 4 cells. A dose-dependent inhibition of the growth rate of the cells was observed. For both cell lines, cytostatic concentrations, expressed in weight of fresh plant, were 0.5 mg/ml culture medium for oak BFMP and 1 mg/ml for apple tree BFMP. However, the action of the two preparations was markedly different on each cell line. Non-viable HTC cells were not stained by trypan blue while non-viable Molt 4 cells were fully colored by this reagent. A lysis of cellular membranes of HTC cells was observed by electron microscopy. Furthermore, oak BFMP inhibited the growth of virus transformed 3T3-SV40 cells more than that of non-transformed 3T3 cells. In contrast to BFMP, non-fermented extracts and a purified mistletoe lectin showed a greater inhibition of the growth of Molt 4 cells than of HTC cells. Samples withdrawn at different times during fermentation gradually lost their inhibitory effect on the growth of Molt 4 cells while their action on HTC cells increased up to the 4th day of fermentation. These results are discussed in relation to the cytotoxic substances of mistletoe already characterized.The bacterially fermented mistletoe preparations, named BFMP in the text, were obtained from the Hiscia Institute, CH-4144 Arlesheim, Switzerland, under the name of Iscador. For oak BFMP, mistletoe was fromQuercus petraea Liebl. andQuercus robur L.; for apple tree BFMP fromMalus domestica Borkh.     

选择性COX-2抑制剂尼美舒利对白血病K562细胞增殖的影响

目的:观察选择性COX-2抑制剂尼美舒利对人类骨髓白血病K562细胞增殖和凋亡的影响。方法:分别以尼美舒利25、50、100μg.mL-1体外处理骨髓白血病K562细胞,采用MTT比色法、流式细胞仪分析技术及DNA片段凝胶电泳等方法,检测尼美舒利对K562细胞增殖和凋亡的影响。结果:尼美舒利剂量依赖性地抑制K562细胞增殖,其中等剂量组(50μg.mL-1)的抑制作用强于阿霉素组(25μg.mL-1);尼美舒利可诱导细胞凋亡,使细胞阻滞于G0/G1期,S期细胞明显减少,其诱导细胞凋亡的作用也呈剂量依赖性(剂量由低至高,凋亡率分别为(3.4±2.8)%,(16.8±1.8)%和(42.7±2.5)%;DNA条带分析也进一步证实了尼美舒利的促凋亡作用。结论:尼美舒利在体外可显著抑制K562细胞增殖,该作用可能与其干扰细胞周期、诱导细胞凋亡有关。     

Effect of propane sultone pretreatment on Friend virus leukemogenesis in mice

Summary Propane sultone (PS) injected i.p. 24 or more hours before Friend leukemia virus increased the incidence of lymphoma in SJL/J mice and at a higher dose increased the incidence of erythroleukemia in B10SJF₁ mice. PS at the same time also decreased hematopoietic stem cell clonogenicity.     

辛伐他汀联合5-FU对K562细胞增殖及凋亡的影响

目的:探讨辛伐他汀(Sim)联合5-FU对白血病K562细胞增殖及凋亡的影响,探讨其作用机制。方法:体外培养人白血病K562细胞,用MTT法观察Sim联合5-FU对细胞的增殖抑制作用,实时荧光定量RT-PCR观察对bcr/abl融合基因mRNA表达水平的影响。流式细胞术、Hoechst33258染色观察Sim与5-FU联合应用诱导细胞凋亡的作用。结果:低浓度的Sim与5-FU联合应用在抑制细胞的增殖,诱导细胞凋亡,均较各单一高浓度用药组的作用明显增强,并且下调bcr/abl融合基因mRNA表达。结论:Sim与5-FU联用具有明显的协同抑制细胞增殖的作用,其作用机制可能与诱导细胞凋亡,下调bcr/abl融合基因的表达有关。     

Sorafenib联合重组人可溶性TRAIL蛋白对K562细胞增殖抑制和凋亡诱导的研究

目的观察比较联合应用重组人可溶性TRAIL蛋白及Sorafenib于人慢性髓系白血病细胞株K562与单独应用时细胞增殖抑制及诱导凋亡的差异。方法通过CCK-8法检测两者对K562细胞的增殖抑制作用;Western-Blot分析TRAIL或与Sorafenib联用对K562细胞的凋亡诱导作用。结果 Sorafenib与TRAIL联合作用于K562细胞时,其细胞的增殖抑制率及凋亡率均显著高于二者单独应用。结论 Sorafenib与TRAIL对K562细胞的增殖抑制及凋亡诱导有增敏及协同作用。     

急性白血病患者白细胞介素-12的表达及临床意义

目的通过检测急性白血病(AL)患者静脉血清中白细胞介素12(IL-12)的含量,探讨IL-12在急性白血病中的临床意义.方法应用定量酶联免疫吸附实验测定10例初诊未治、10例缓解期、5例复发患者和9例正常对照血清中IL-12的含量.结果对照组的IL-12水平(58.96±38.11)ng/L与初诊复发组(初诊未治组与复发组的合称)(32.51±14.58)ng/L、缓解组(71.67±119.09)ng/L之间均有显著性差异(P<0.05).结论IL-12与AL的病情变化有一定的关系.     

Logistic回归预测白血病病人生存时间

为了对白血病患者的生存时间进行预测,帮助医学工作者制定相应的医疗方案,借助于Logistic回归模型,对50名白血病人的生存资料进行建模分析.结果表明:外辕血中的细胞数对患者生存时间的影响不显著,淋巴结浸润等级和出院后有无巩固治疗对患者的生存时间影响显著,巩固治疗比没有巩固治疗生存时间提高了约9.6倍.     

基于L_1范数最小化的逆协方差矩阵估计

由于在高维空间中,基于固定维数的经典方法和结果不再适用,样本协方差矩阵不可逆,估计逆协方差矩阵时存在不稳定、计算成本高和非精确等问题,提出了一种L1范数最小化方法来有效估计高维逆协方差矩阵即精确矩阵.当总体分布满足指数类型条件或者多项式类型条件时,所提估计方法在各种范数下的收敛速率优于其他现存的方法.经分析验证,所提方法为凸优化问题,可采用交替方向乘子算法来解决.之后通过R语言在模拟数据和实际数据下进行仿真分析,并与Glasso方法对比逆协方差的估计性能和图恢复性能,结果表明所提估计方法准确率高、计算成本低.最后,将所提估计方法用来分析白血病数据集,并运用聚类分析对白血病人进行分类.