IL-6/STAT3信号通路与结直肠癌关系的研究进展

目的:探讨白细胞介素-6(interleu-kin-6,IL-6)/信号传导子及转录激活子3(signal transducer and activator of transcrip-tion3,STAT3)通路与结直肠癌(colorectalcancer,CRC)关系的研究进展。方法:以CRC和IL-6;CRC和STAT3为关键词,检索1989-2009年PubMed及CNKI期刊全文数据库,分别检索到英文文献438和76篇及中文文献1 824和391篇。检索到纳入标准:1)IL-6/STAT3通路与CRC发病机制相关文献;2)IL-6/STAT3通路与CRC诊疗相关研究。粗选有96篇关于IL-6/STAT3通路与CRC关系的研究文章,根据纳入标准精选33篇文献纳入。结果:IL-6是一种多效细胞因子。研究证实,IL-6在肿瘤患者外周血和肿瘤组织中均呈现高表达。IL-6与其相应受体结合,受体复合物结合gp130后活化STAT3。近年研究发现CRC中存在STAT3过度活化和功能紊乱现象。IL-6和STAT3的变化最终诱导IL-6/STAT3通路下游与炎症、癌症密切相关分子的表达。结论:对IL-6/STAT3通路...     

IL-6/STAT3信号传导通路及其在肿瘤靶向治疗中的作用

白细胞介素-6(IL-6)与肿瘤患者的分期、预后、转归以及对化疗药物的敏感性有关,且在患者的肿瘤组织及血清中常呈过表达.IL-6主要通过介导信号转换和转录激活因子3(STAT3)信号传导通路(IL-6/STAT3信号传导通路)来调节肿瘤细胞的增殖和分化.因此,IL-6/STAT3信号传导通路的阻断,对肿瘤具有潜在治疗意...     

通讯作者：花宝金(1964-),男,黑龙江人,主任医师,博士研究生导师,研究方向: 中医药防治肿瘤复发转移。稿件联系人：蒋树龙,E-mail:jnsljiang@163.com。联系电话：13506383007。

【】　目的：总结JAK2/STAT3/SOCS3信号通路的作用特点及其与肿瘤转移潜能的最新研究进展。方法：应用PubMed及CNKI期刊全文数据库,以“JAK2、STAT3、SOCS3、肿瘤和信号转导”为关键词,检索2000-01~2013-10的相关文献,共检索到英文文献343篇,中文文献66篇。文献纳入标准：１)JAK2/STAT3/SOCS3信号通路的生物学特征及作用机制;２)JAK2/STAT3/SOCS3信号通路与肿瘤微环境的关系及其与肿瘤侵袭转移之间的内在联系。根据纳入标准符合条件的30篇。结果：JAK2/STAT3信号通路的激活参与了肿瘤发生、发展、侵袭和转移等多个环节;SOCS3负性调控JAK2/STAT3通路,从而抑制肿瘤的增殖和生长;STAT3信号通路的激活促成了肿瘤炎性微环境的形成,参与了肿瘤血管生成、上皮间质转化(EMT)、细胞外基质(ECM)降解等多个环节,在肿瘤的侵袭和转移过程中发挥重要作用。结论：JAK2/STAT3/SOCS3信号通路与肿瘤转移密切相关,针对JAK2/STAT3/SOCS3信号通路多靶点干预是肿瘤防治研究的一个新方向。     

Notch信号通路介导EMT与肿瘤侵袭转移的研究进展

摘 要：Notch信号通路是一个在进化过程中高度保守的信号通路,它广泛参与细胞的增殖、分化及凋亡过程,在肿瘤的发生发展,侵袭与转移过程中发挥着重要作用。上皮间质转化（epithelial-mesenchymal transition,EMT)与恶性肿瘤的局部浸润和远处转移密切相关,研究证明介导EMT在此过程中的细胞内信号途径主要有以下几种,分别是：PI3K/AKT途径、TGF-β信号途径、Wnt信号通路、Hedgehog通路、IL-6/STAT3通路、Notch信号通路等。全文就Notch信号通路介导EMT在肿瘤侵袭转移中的作用及其分子机制的研究进展作一综述。     

靶向STAT3 信号通路抗肿瘤治疗策略的研究进展

转录信号转导子与激活子3（STAT3）持续活化及异常高表达,与肿瘤的发生发展及不良预后密切相关,已成为新型抗瘤药物的潜在靶标。目前,靶向STAT3 信号转导通路的肿瘤治疗策略主要包括小分子干扰RNA、特异性寡核苷酸、正向调控促癌基因敲除等核酸类抑制干预,JAK-2 抑制剂、酪氨酸及其激酶抑制剂、细胞因子及受体拮抗剂等STAT3 上游信号阻断及负调控蛋白表达促进,STAT3 负显性蛋白、二聚体拮抗剂等STAT3/pSTAT3 特异性抑制。另外,天然药物有效成分及其他具有靶向STAT3信号的药剂,亦可通过下调STAT3 蛋白水平、抑制蛋白磷酸化、靶向STAT3 上游信号转导及下游靶分子阻抑肿瘤细胞生长增殖和侵袭转移。     

白细胞介素-6/信号转导和转录激活因子3信号通路在大细胞肺癌NL9980细胞系增殖中的作用及机制

背景与目的：白细胞介素-6/信号转导和转录激活因子3(IL-6/STAT3)信号通路在很多恶性肿瘤中存在过度激活及表达,包括白血病、头颈部鳞状细胞癌多发性黑色素瘤、乳腺癌以及前列腺癌等,但其在大细胞肺癌中的研究少见。该研究旨在探索大细胞肺癌NL9980细胞系中IL-6/STAT3信号通路在细胞增殖中的作用及其机制。方法：将外源性IL-6设立5个浓度梯度(终浓度分别为0、1.0、5.0、10.0和20.0 ng/mL),分别对NL9980细胞系进行干预。运用噻唑蓝(MTT)法观察细胞增殖活力改变,并确立IL-6干预的最佳浓度。采用RT-PCR技术检测IL-6/STAT3相关基因及其下游调控基因Bcl-2、VEGF和CYCD1的mRNA表达量,并将IL-6/STAT3相关基因与下游基因做相关性分析。结果：外源性IL-6可促进NL9980细胞系的增殖,其最佳干预浓度为5 ng/mL(F=8.11,P<0.05)。信号通路相关基因IL-6及STAT3的mRNA表达量均以5 ng/mL组最高,分别为4.78±0.09和5.17±0.05(P<0.05);下游调控基因中,Bcl-2、VEGF及CYCD1的mRNA表达量均在5 ng/mL组最高,分别为4.52±0.14、4.12±0.12和3.98±0.17,其余浓度组与对照组相比,差异无统计学意义(P>0.05)。相关性分析表明,下游基因中Bcl-2、VEGF、CYCD1与IL-6(r=0.952,r=0.836,r=0.880)和STAT3(r=0.995,r=0.746,r=0.800)呈正相关性。结论：IL-6可促进大细胞肺癌NL9980细胞系的增殖,其机制可能是通过活化IL-6/STAT3信号通路并上调相关基因Bcl-2、VEGF和CYCD1的表达来实现的。     

STAT3信号通路影响肿瘤放射敏感性的研究进展

信号转导与转录激活因子3（STAT3）在多数肿瘤中处于过表达状态,其与肿瘤增殖、分化及凋亡密切相关,该信号通路激活能促进肿瘤的生长及侵袭。新近研究发现STAT3异常活化可降低肿瘤的放射敏感性,促使肿瘤逃避射线的杀伤作用。肿瘤中STAT3的表达情况可用来评价放疗疗效和判断预后,抑制该通路能逆转肿瘤放疗耐受。对STAT3信号通路不断深入研究,可为肿瘤的靶向治疗提供更多新思路。     

STAT3与肿瘤的靶向治疗

信号转导及转录活化因子3（STAT3）是STAT家族成员之一,也是肿瘤组织中的常见通路。STAT3与肿瘤的增生、凋亡、侵袭、迁徙、血管生成和免疫逃逸等关联。因此STAT3信号通道成为肿瘤治疗的一个潜在的作用靶点。     

STAT3与肿瘤的关系

目前在分子水平及信号传导通路方面研究疾病的病因和发病机制已成为国内外研究的热点.其中,STAT3信号传导途径参与体内多种细胞因子的信号转导过程,在调节细胞的增殖、分化、存活和凋亡中具有重要作用,是体内多条致癌性信号传导通路汇聚的焦点,在多种肿瘤细胞中均发现了STAT3蛋白的持续性激活.研究表明,STAT3通路的激活与肿瘤的发生、发展及恶性生物学行为密切相关,并有望成为肿瘤治疗的新靶点.     

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.     

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.     

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.     

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.