Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate

Kinesin-5 inhibitors (K5I) are promising antimitotic cancer drug candidates. They cause prolonged mitotic arrest and death of cancer cells, but their full range of phenotypic effects in different cell types has been unclear. Using time-lapse microscopy of cancer and normal cell lines, we find that a novel K5I causes several different cancer and noncancer cell types to undergo prolonged arrest in monopolar mitosis. Subsequent events, however, differed greatly between cell types. Normal diploid cells mostly slipped from mitosis and arrested in tetraploid G(1), with little cell death. Several cancer cell lines died either during mitotic arrest or following slippage. Contrary to prevailing views, mitotic slippage was not required for death, and the duration of mitotic arrest correlated poorly with the probability of death in most cell lines. We also assayed drug reversibility and long-term responses after transient drug exposure in MCF7 breast cancer cells. Although many cells divided after drug washout during mitosis, this treatment resulted in lower survival compared with washout after spontaneous slippage likely due to chromosome segregation errors in the cells that divided. Our analysis shows that K5Is cause cancer-selective cell killing, provides important kinetic information for understanding clinical responses, and elucidates mechanisms of drug sensitivity versus resistance at the level of phenotype.     

抗HPV16E7－ribozyme和靶RNA相互作用的计算机分析

应用计算机分析了抗ＨＰＶ１６Ｅ７－ｒｉｂｏｚｙｍｅ的体外切割反应结果，发现ｒｉｂｏｚｙｍｅ和靶ＲＮＡ的二级结构及其能量变化能影响ｒｉｂｏｚｙｍｅ的切割活性。根据锤头结构ｒｉｂｏｚｙｍｅ的能量变化模型，对抗ＨＰＶ１６Ｅ７－ｒｉｂｏｚｙｍｅ和靶ＲＮＡ在痘苗表达体系及稳定表达体系中的相互作用，进行计算机模拟分析。结果表明，计算机分析ｒｉｂｏｚｙｍｅ和靶ＲＮＡ在细胞内的相互作用，可以指导ｒｉｂｏｚｙｍｅ的设计和在体内的应用研究。     

隐血珠在上消化道癌初筛普查中实用价值研究

目的通过对隐血珠初筛人群及癌患者5年、10年随访,进一步证实隐血珠对上消化道癌初筛普查的实用价值。方法空腹时吞入隐血珠,3～5分钟拉出,观察珠内试纸的变化,黄色为阴性(-),浅蓝色为(+),蓝色为(++),深蓝色为(+++),5年、10年后对隐血珠初筛人群及癌患者通过三级防癌网络进行全员随访。结果初筛普查31927人,阳性组3347人做胃镜,经病理确诊为癌患者125人,癌检出率3.74％;阴性组645人做胃镜,确诊癌患者9人,癌检出率1.4％,两组中早期癌患者共78人,占62.4％,性别、年龄、隐血珠反应均是影响癌检出率的因素,经5年及10年两次全员随访资料统计,隐血珠初筛阳性组癌发率均明显高于阴性组,癌患者5年生存率67.2％,10年生存率为55.2％,性别、年龄、隐血珠反应也是影响筛查人群上消化道癌发生率的因素。结论隐血珠在上消化道癌初筛普查中有肯定的实用价值,值得推广。     

耳穴压豆配合玻璃酸钠滴眼液治疗干眼的随机对照研究

目的 观察耳穴压豆配合治疗对于眼患者临床客观指标的影响.方法 将120例轻、中度干眼患者随机分为治疗组60例、对照组60例.对照组予0.1％玻璃酸钠滴眼液治疗,治疗组在对照组治疗基础上,予王不留行籽耳穴压豆.观察泪膜破裂时间(break-up time of tears,BUT)、角膜荧光染色(fluoresce st...     

对93例静脉输液反应的分析及管理对策

目的 :减少静脉输液的热原反应。方法 :分析 93例静脉输液热原反应情况。结果 :输液反应管理中存在以下问题 :登记不全 ;取样范围局限和热原检测比例不足 ;两种药物热原检测方法—家兔试验法与鲎试验法的结论有不一致性 ;医务人员思想认识模糊 ,原因排查不力。结论 :健全医院输液反应管理制度 ,做好各种原始记录 ,在输液反应热原检测中 ,鲎试验法更为可靠及时     

复杂性室性心律失常对老年充血性心力衰竭预后的影响

目的探讨复杂性室性心律失常对老年充血性心力衰竭(CHF)预后的影响。方法172例老年充血性心力衰竭(CHF)根据24hCCU或Holter检测结果,诊断为复杂性室性心律失常者(阳性组)58例,与无复杂性室性心律失常(阴性组114例)进行对比研究。终点:患者死亡或治愈出院日期,并以此计算死亡率及生存率。结果阳性组总体死亡率(51.72%)及猝死率(27.59%)明显高于阴性组(29.82%和7.89%)(P<0.01);阳性组86.4%的死亡者临终心电图表现为室速或室颤,而阴性组则以慢性心律失常或停搏为多(P<0.01);阳性多源性室早及R-ON-T室早猝死率明显高于对照组(16.63%和20.00%)(P<0.01及0.05)。结论老年重度CHF并复杂性室性心律失常时总死亡率、猝死率均明显增加,其中成对室早及非持续性心动过速的危险性最大。可能作为老年CHF患者总死亡率增加的独立预测指标。     

核糖核酸阻抑家兔肝纤维化的作用机制探讨

通过电镜、生化、免疫学等方法观察了ＲＮＡ对感染尾蚴兔的作用。结果表明，ＲＮＡ能使感染尾蚴兔肝细胞核仁增大，粗面内质网及其颗粒增多，肝ＲＮＡ含量增加，血浆ＴＮＦａ降低。分析结果提示ＲＮＡ是通过其模板作用和基因调控作用、免疫调节作用等来阻抑兔肝纤维化进展加重的。     

Understanding bistability in complex enzyme-driven reaction networks

Much attention has been paid recently to bistability and switch-like behavior that might be resident in important biochemical reaction networks. There is, in fact, a great deal of subtlety in the relationship between the structure of a reaction network and its capacity to engender bistability. In common physicochemical settings, large classes of extremely complex networks, taken with mass action kinetics, cannot give rise to bistability no matter what values the rate constants take. On the other hand, bistable behavior can be induced in those same settings by certain very simple and classical mass action mechanisms for enzyme catalysis of a single overall reaction. We present a theorem that distinguishes between those mass action networks that might support bistable behavior and those that cannot. Moreover, we indicate how switch-like behavior results from a well-studied mechanism for the action of human dihydrofolate reductase, an important anti-cancer target.