肿瘤与纺锤体检查点的研究现状

纺锤体检查点阻滞细胞进入分裂后期直到所有染色体着丝点正确与微管联接 ,确保染色体均等分配 ,维持基因组稳定性。纺锤体检查点的分子调控机制已初步建立。许多肿瘤细胞存在纺锤体检查点功能缺陷 ,但纺锤体检查点基因突变异常罕见 ,需要深入了解肿瘤纺锤体检查点调控机制 ,为肿瘤防治提供新的有效策略     

Aurora激酶与人类肿瘤的研究进展

Aurora蛋白激酶家族，包括Aurora-A、Aurora-B和Aurora-C，在细胞有丝分裂期过程中发挥着重要作用。Aurora-A定位于中心体和纺锤体，主要参与中心体的成熟、分离和纺锤体形成，还参与p53通路、细胞凋亡和有丝分裂的调节等。Aurora-A在多种肿瘤组织中存在着高表达。它的高表达可能会导致基因的不稳定和肿瘤的发生，与某些肿瘤的预后相关。最近对其三维结构的测定推进了对激酶抑制剂的研究，希望能够发现新的抗癌因子。Aurora-B参与染色体调节、分离，并在纺锤体检查点等方面发挥重要作用。Aurora-C和AuroraB共同参与哺乳动物有丝分裂染色体分离和胞质分裂。     

染色体不稳定分子机制及其与肿瘤发生研究的新进展

绝大多数肿瘤特别是实体瘤细胞常表现为染色体不稳定性。本文从纺锤体检测点、多中心体、细胞周期检测点、DNA双链断裂、异常端粒、甲基化等角度综述了染色体不稳定性产生的可能分子机制,以及其与肿瘤发生的关系。这些研究为肿瘤发生分子机制的研究拓展了新的视野,为肿瘤诊断、治疗、分型、预后提供了新的思路。     

Aurora激酶与人类肿瘤的研究进展

Aurora蛋白激酶家族,包括Au-rora-A、Aurora-B和Aurora-C,在细胞有丝分裂期过程中发挥着重要作用。Aurora-A定位于中心体和纺锤体,主要参与中心体的成熟、分离和纺锤体形成,还参与p53通路、细胞凋亡和有丝分裂的调节等。Auro-ra-A在多种肿瘤组织中存在着高表达。它的高表达可能会导致基因的不稳定和肿瘤的发生,与某些肿瘤的预后相关。最近对其三维结构的测定推进了对激酶抑制剂的研究,希望能够发现新的抗癌因子。Aurora-B参与染色体调节、分离,并在纺锤体检查点等方面发挥重要作用。Auro-ra-C和Aurora-B共同参与哺乳动物有丝分裂染色体分离和胞质分裂。     

ECRG2基因缺失导致纺锤体检测点功能缺陷

目的 观察ECRG2基因对纺锤体检测点功能的影响.方法 利用基因敲除和免疫荧光染色技术观察ECRG2基因在细胞内的定位及生物学功能.结果 ECRG2基因在有丝分裂间期分布于中心体、有丝分裂期分布于着丝粒处,可能参与中心体复制和纺锤体检测点功能.siRNA技术敲除ECBG2基因细胞导致纺锤体检测点功能丧失,在nocodazole处理时无法阻断细胞于有丝分裂期而进入下一细胞周期,最终导致染色体不稳定性和非整倍体细胞出现.结论 ECRG2在纺锤体检测点中起重要作用,对确保染色体稳定性必不可少;ECRG2基因的缺失可能是肿瘤细胞染色体不稳定性和非整倍体细胞产生的重要原因.     

口腔鳞癌细胞染色体不稳定潜在机制的探讨

目的:探讨口腔鳞癌细胞染色体不稳定形成的潜在机制.方法:对7株非整倍体口腔鳞状细胞癌(OSCC)细胞系细胞,采用荧光活化细胞分类(FACS)及免疫荧光染色(IF)的方法,观察非整倍体OSCC细胞有丝分裂检查点(又称纺锤体检查点)功能及中心体状况.结果:7株非整倍体OSCC细胞系细胞经过0.2μg/ml噻氨酯哒唑(Nocodazole)处理18小时后,都出现了高比例分裂中期(G2/M)细胞的累积,提示这些细胞有丝分裂检查点功能正常:而中心体异常(数目增多及形态的异常)可以在所有非整倍体OSCC细胞系中观察到,异常细胞百分率04%～18.8%.结论:OSCC细胞CIN表型与有丝分裂检查点功能异常之间可能无直接机制上的联系,但中心体异常可能是OSCC细胞染色体不稳定形成的潜在机制之一.     

α粒子诱发细胞癌变的纺锤体检测点功能分析

目的：通过分析人支气管上皮细胞BEP2D和其α粒子诱发的癌变细胞系BERP35T1和BERP35T4的纺锤体检测点功能，探讨纺锤体检测机制变化在辐射致癌中的作用。方法：用噻氨酯哒唑药物破坏细胞的微管结构，导致纺锤体形成受阻，在光学显微镜下计数有丝分裂细胞。结果：本实验观察的辐射诱发癌变细胞系中有的染色体数目相对稳定，有的不稳定，其中表现为多倍体细胞比例增高。通过分析纺锤体检测点机制，发现染色体数目异常(多倍体)比例高的癌变细胞BERP35T4(40％)在噻氨酯哒唑药物作用后12—24h，有丝分裂指数(MI)明显低于亲本BEP2D细胞和另一癌变细胞系BERP35T1，后二者细胞的多倍体率较低(5％)。结论：纺锤体检测点机制异常与α粒子照射诱发恶性转化细胞BERP35T4的染色体不稳定性相关。     

HPV 16型E6蛋白诱导PHK多倍体的形成与消除细胞纺锤体检查点无关水

目的:人乳头瘤病毒16型(human papillomavirus,HPV 16)与包括宫颈癌在内的多种肿瘤的发生明确相关.诱导宿主基因组不稳定性可能是HPV 16致瘤的重要机制之一.本研究对HPV 16型E6蛋白诱导人原代角质形成细胞(primary human keratinocytes,PHK)形成多倍体以及对PHK有丝分裂纺锤体检查点的影响进行初步的探索.方法:取正常人包皮组织,分离表皮,常规方法培养PHK.脂质体介导法将pBabe一16 E6质粒转染逆转录病毒包装细胞PA317,挑选G418抗性克隆,检测病毒滴度,将表达HPV 16型E6蛋白的高滴度逆转录病毒感染PHK.通过逆转录PCR法和免疫印迹法证实HPV 16 E6成功感染PHK.PHK经Nocodazole处理后,利用流式细胞仪分析多倍体形成,于不同时间点收集细胞、固定,进行抗磷酸化组蛋白染色,利用流式细胞仪分析细胞有丝分裂指数差异.结果:HPV 16型E6成功感染PHK,并呈功能性表达.HPV 16型E6可诱导PHK形成多倍体,表达E6蛋白的PHK和对照细胞以相似的动力学进入和退出有丝分裂.结论:HPV 16型E6对PHK有丝分裂过程中的纺锤体检查点无直接影响,鉴于有丝分裂后期检查点在细胞有丝分裂过程中较持久和严格的作用,本研究结果提示,对有丝分裂后期检查点的作用可能是HPV 16型E6蛋白诱导宿主细胞多倍体形成的重要机制.为进一步探讨HPV相关肿瘤的分子发生机制.奠定了一定基础.     

HPV 16型E6蛋白诱导PHK多倍体的形成与消除细胞纺锤体检查点无关

目的：人乳头瘤病毒16型（human papillomavirus,HPV 16）与包括宫颈癌在内的多种肿瘤的发生明确相关。诱导宿主基因组不稳定性可能是HPV16致瘤的重要机制之一。本研究对HPV16型E6蛋白诱导人原代角质形成细胞（primary human keratinocytes,PHK）形成多倍体以及对PHK有丝分裂纺锤体检查点的影响进行初步的探索。方法：取正常人包皮组织,分离表皮,常规方法培养PHK。脂质体介导法将pBabe-16E6质粒转染逆转录病毒包装细胞PA317。挑选G418抗性克隆,检测病毒滴度,将表达HPV16型E6蛋白的高滴度逆转录病毒感染PHK。通过逆转录PCR法和免疫印迹法证实HPV16E6成功感染PHK。PHK经Nocodazole处理后,利用流式细胞仪分析多倍体形成,于不同时间点收集细胞、固定,进行抗磷酸化组蛋白染色,利用流式细胞仪分析细胞有丝分裂指数差异。结果：HPV16型E6成功感染PHK,并呈功能性表达。HPV16型E6可诱导PHK形成多倍体,表达E6蛋白的PHK和对照细胞以相似的动力学进入和退出有丝分裂。结论：HPV16型E6对PHK有丝分裂过程中的纺锤体检查点无直接影响,鉴于有丝分裂后期检查点在细胞有丝分裂过程中较持久和严格的作用,本研究结果提示,对有丝分裂后期检查点的作用可能是HPV16型E6蛋白诱导宿主细胞多倍体形成的重要机制。为进一步探讨HPV相关肿瘤的分子发生机制奠定了一定基础。     

Polo样激酶抑制剂在肿瘤治疗中的应用

Polo样激酶(PLK)是一类高度保守的丝氨酸/苏氨酸蛋白激酶,在细胞有丝分裂调控点上发挥重要作用.大约80％的人类肿瘤都表达高水平的PLK,PLK在肿瘤中过度表达而在正常细胞中很少表达的特性使之成为一种很好的抗癌靶点.PLK抑制剂可以干扰癌细胞有丝分裂的不同阶段,如中心体成熟、纺锤体形成、染色体分离、胞质分裂等,导致有丝分裂停滞,严重干扰细胞周期进程,最终导致癌细胞死亡.当前,有一些PLK抑制剂处于临床前研发阶段,有些正处在临床试验阶段.全文着重论述近年来PLK抑制剂在肿瘤治疗中的应用.     

Ringworm in animals in a farm in Assiut

Bericht über das Auftreten von Hautmykosen bei Tieren auf der Farm der Landwirtschaftlichen Fakultät der Universität Assiut. Von 70 Kälbern waren 42 pilzkrank, davon 22 durch T. mentagrophytes, 20 durch T. verrucosum. Von 180 Kühen waren 8 pilzbefalien, sämtlich durch T. mentagrophytes. Von 2 kranken Bullen wurde T. verrucosum isoliert. Auch die 3 Pferde und 2 Maultiere der Farm waren pilzinfiziert; Erreger war in diesen Fällen T. equinum. Auch ein Kalb war von T. equinum befallen. Die gleiche Pilzart wurde ferner von 3 Tierpflegern isoliert, die Pilzherde am Hals und an den Armen aufwiesen.     

Statistical challenges in preprocessing in microarray experiments in cancer

Many clinical studies incorporate genomic experiments to investigate the potential associations between high-dimensional molecular data and clinical outcome. A critical first step in the statistical analyses of these experiments is that the molecular data are preprocessed. This article provides an overview of preprocessing methods, including summary algorithms and quality control metrics for microarrays. Some of the ramifications and effects that preprocessing methods have on the statistical results are illustrated. The discussions are centered around a microarray experiment based on lung cancer tumor samples with survival as the clinical outcome of interest. The procedures that are presented focus on the array platform used in this study. However, many of these issues are more general and are applicable to other instruments for genome-wide investigation. The discussions here will provide insight into the statistical challenges in preprocessing microarrays used in clinical studies of cancer. These challenges should not be viewed as inconsequential nuisances but rather as important issues that need to be addressed so that informed conclusions can be drawn.     

Trends in zygomycosis in children

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.     

Dermatomycosis in Goats in India

Summary: In an extensive survey involving 2176 goats 1.56% of goats manifested clinical lesions of ringworm infection. Animals below the age of 6 months were affected most (4.20%). The incidence of infection was higher during the winter months. T. verrucosum, T. mentagrophytes and M. gypseum were isolated from the skin scrapings of 12, 4, and 2 goats respectively. It is suggested that the infected animals could be a source of disease to human population in which the zoophilic dermatophyte invasion is characterized by severe inflammatory lesions of the skin. The zoonotic importance of different dermatophytes is stressed.
Zusammenfassung: In einer ausgedehnten Untersuchung an 2176 Ziegen wurden bei 1,56% klinische Zeichen einer Hautmykose festgestellt. Tiere, die jühger als 6 Monate alt waren, zeigten mit 4,20% am häfigsten Krankheitssymptome. In den Wintermonaten war die Erkrankungshäufigkeit am gröBten. T. vermcosum, T. mentagrophytes and M. gypseum wurden jeweils von 12,4 bzw. 2 Ziegen isoliert. Die inflzierten Tiere köinnen eine Infektionsquelle für die menschliche Bevölkerung darstellen und dort Mykosen mit stark entzündlichen Veränderungen auslösen. Die Bedeutung verschiedener Dermatophyten als Erreger von Zoonosen wird hervorgehoben.     

Hemoglobin in lymphogranulomatosis in children

The peculiarities of hemoglobin content and properties in lymphogranulomatosis were studied in children by different methods. In most patients the content of fetal hemoglobin and methhemoglobin was found to increase and the rate of ferricyanide oxidation of hemoglobin also increases. Simultaneously, the rate of non-homogenicity of basic hemoglobin fractions was observed to increase on account of immunologically different components.     

Sex hormones in women in rural China and in Britain

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.