黑色素瘤缺乏因子2炎症小体在肿瘤中作用的研究进展

黑色素瘤缺乏因子2(AIM2)是非特异免疫系统中的一种感受分子,它可对细胞质中的核酸DNA进行特异性识别,启动炎症小体,从而介导炎症反应.这种炎症反应与多种疾病相关,与肿瘤的发生和发展也有一定的关联性.不同肿瘤的发病机制不同,AIM2炎症小体对不同种类肿瘤的调控机制也存在差异.本文主要从AIM2炎症小体的组成、活化机制及与肿瘤的关系方面进行综述,总结了AIM2炎症小体与结直肠癌、肝癌、非小细胞肺癌(NSCLC)和口腔鳞状细胞癌(OSCC)的关系,并提出了几个待解决的问题:AIM2炎症小体是否也与甲状腺癌的发生和发展有关,AIM2炎症小体在甲状腺癌中的表达是否与甲状腺癌的病理类型、转移情况、分期情况相关.     

AIM2在结直肠癌中的作用机制及对免疫治疗的意义

黑色素瘤缺乏因子2(absent in melanoma 2, AIM2)定位于细胞质中,可作为模式识别受体感受释放到胞质中的dsD- NA,通过与ASC接头蛋白结合形成炎性小体,从而激活Caspase-1促进炎性细胞因子的分泌和成熟,启动固有免疫应答或细胞焦 亡(pyroptosis)。AIM2被认为是一种肿瘤抑制因子,在多种肿瘤中有异常表达,在肿瘤的发生发展中起到重要作用,能调控急性 电离辐射和化疗引发的结直肠炎症。炎性小体在维持肠道内环境稳态的过程中也起到重要的作用。AIM2能调控细胞周期,抑 制细胞异常增殖,PIK3/Akt通路在结直肠癌（colorectal cancer, CRC)的发生发展中起到重要作用。AIM2能促使IFN-γ和IL-1β分 泌,激发抗肿瘤免疫应答。AIM2还能调控肠道干细胞扩增,调节肠道菌群。AIM2的缺失与CRC的不良预后显著相关,其表达 在CRC的发生发展中起到重要的预后价值。研究AIM2炎性小体在抗肿瘤免疫应答中的作用,对探索和优化CRC免疫治疗过程 的方法有着重要的意义。     

NLRP1 炎症小体与肿瘤研究进展

炎症小体是由多种蛋白质构成的复合体，是天然免疫系统的主要组成部分。炎性小体的形成能激活半胱天冬氨酸酶-1（Caspase-1），进而引起细胞因子前体pro-IL-1β和pro-IL-18成熟和分泌并诱导细胞焦亡。NOD样受体蛋白1（nod like receptor protein 1，NLRP1）炎症小体由、接头蛋白ASC（apoptosis-associated speck-like protein containing a CARD，ASC）和效应蛋白Caspase-1构成，其激活失调与肿瘤发病机制有关，但目前在肿瘤发生和发展中的作用仍然存争议。本文就NLRP1炎症小体与肿瘤的研究进展作一综述。       

细胞焦亡诱导在抗肿瘤治疗中应用的研究进展

细胞焦亡是近年来发现的一种新型细胞死亡的方式,是一种受焦孔素（GSDM）家族调控的炎症性程序性细胞死亡,其主要特征是膜穿孔、细胞肿胀及细胞破裂。细胞焦亡发生的机制分为由GSDMD介导的Caspase-1和Caspase-4/-5/-11依赖性经典炎症小体途径和由GSDME介导的Caspase-3和颗粒酶依赖性非经典炎症小体途径等。近年来研究显示,细胞焦亡具有抑制和促进肿瘤发生发展的双重作用,并且细胞焦亡的诱导在抗肿瘤免疫治疗中也发挥双重效应：一方面通过促进炎症因子释放,形成肿瘤微环境,抑制抗肿瘤免疫,另一方面则通过引发抗肿瘤炎症反应抑制肿瘤细胞的增殖。此外,细胞焦亡的诱导在化疗及其他联合治疗中也发挥着重要作用。进一步研究发现,中药及其提取物调控细胞焦亡的诱导对于治疗肿瘤至关重要。     

NLRP3炎性小体诱导的焦亡及其在肿瘤中的作用

摘 要：程序性细胞死亡（PCD）是指细胞通过基因编码方式发生了自发性细胞死亡,包括凋亡、焦亡、自噬、坏死性凋亡（又称程序性坏死） 4种方式,其中焦亡是近期发现的一种全新的程序性细胞死亡模式。与凋亡不同,焦亡通过诱导细胞膜上膜孔的形成,引起细胞外炎症反应。目前已经发现了4种焦亡诱导途径。诱导焦亡发生需要多个细胞因子的介导,而炎性小体是大多数焦亡激活途径所必需的。炎性小体是一种多聚体蛋白质复合物,其中NOD样受体蛋白3（NLRP3）炎性小体是目前研究较为深入的一种炎性小体,它在不同类型的肿瘤中介导焦亡的发生。NLRP3炎性小体诱导的焦亡对不同肿瘤的影响具有特异性。在某些肿瘤,如胃癌、结直肠癌和肺癌中,焦亡诱导的细胞炎性反应促进了肿瘤的发展;而在另一些肿瘤中,如肝细胞癌和部分直肠癌中,焦亡诱导的细胞炎性反应则抑制了肿瘤的发展。由于在肿瘤中表现出了“双刃剑”的作用,NLRP3炎性小体诱导的焦亡受到了广泛关注。全文就焦亡的机制和途径,以及NLRP3炎性小体介导的焦亡在肿瘤中的作用作一综述。     

COX-2/PGE2在肿瘤发生发展和重塑肿瘤微环境中的研究进展

癌症相关炎症（cancer-related inflammation，CRI）在癌症的发生发展中发挥重要作用，前列腺素E2（prostaglandin E2，PGE2）是炎症环境中最为丰富的类花生酸脂质，也是肿瘤微环境中具有免疫调节功能的脂类代谢产物。目前，PGE2合成途径阻断药物联合抗肿瘤药物在肿瘤治疗方面取得一定成效。因此，了解肿瘤微环境中PGE2合成途径的调控环节及其对肿瘤发生发展的作用机制，可为肿瘤防治找寻新方向、提供新靶点。本文就近年来PGE2在肿瘤发生发展和重塑微环境的研究进展进行概述。      

基于细胞焦亡机制的肿瘤免疫治疗新策略

细胞焦亡是近年来发现的一种全新的调节性细胞死亡形式,在肿瘤免疫中发挥重要作用。肿瘤发生发展进程中的细 胞焦亡包含免疫细胞焦亡（ICP）和肿瘤细胞焦亡（CCP）两种类型,并可能发挥促癌或抑癌作用。Caspase-1介导的经典途径和 caspase-4/5/11介导的非经典途径均可以介导ICP的发生,ICP参与的肿瘤免疫中,炎症小体和细胞因子IL-18、IL-1β发挥了重要 作用。Caspase-3和颗粒酶B切割并激活GSDME途径介导了CCP的发生,在肿瘤发生过程中自发且持久的CCP促进肿瘤生长, 而在化疗等过程中GSDME激活介导的CCP则具有显著的抑癌作用。细胞焦亡的发生可以刺激肿瘤微环境中的炎症反应,提高 肿瘤细胞的免疫原性,促进抗肿瘤免疫的发生。因此,细胞焦亡及其引发的炎症反应在肿瘤免疫中发挥重要作用,对该领域的研 究可能为抗肿瘤免疫治疗提供新思路。     

TFPI-2对恶性肿瘤细胞增殖凋亡侵袭转移调控作用的研究进展

组织因子途径抑制物-2（tissue factor pathway inhibitor-2,TFPI-2）是具有库尼（Kunitz）结构域的丝氨酸蛋白酶抑制剂。新近发现,TFPI-2在恶性肿瘤中表达降低,并与肿瘤转移、侵袭等恶性生物学行为密切相关。该分子表达的分子调控机制包括启动子CpG岛超甲基化、ERK1/2信号途径、JNK信号途径等。TFPI-2的主要功能体现在维持肿瘤微环境的稳定性,抑制肿瘤细胞的生长、侵袭和转移。目前认为,TFPI-2在调节细胞增殖、凋亡以及血管生成拟态方面也发挥重要作用。本文就TFPI-2在肿瘤中的表达及调控机制、细胞凋亡、血管生成中作用进行综述,为其在肿瘤的预防、诊断及基因治疗中开展深入研究提供理论基础。      

MyD88在肿瘤免疫耐受及免疫治疗中的研究进展

摘 要：MyD88作为一种通用的信号衔接蛋白，调节大多数Toll样受体（TLR）和白细胞介素1受体（IL-1R）级联的信号传导，参与介导先天免疫，调节炎症微环境和肿瘤微环境。通过TLR/MyD88信号途径，MyD88直接或间接地影响多种下游的免疫因子分泌，诱导肿瘤细胞和/或免疫细胞分泌蛋白或表面分子改变，同时引起肿瘤组织局部免疫细胞种类、数量及功能的改变，导致炎症微环境恶化及肿瘤微环境重塑，最终引起肿瘤免疫耐受和免疫逃逸。MyD88在肿瘤免疫治疗中具有双重作用，一方面通过分泌免疫抑制因子，抑制疗效；另一方面将MyD88信号与嵌合抗原受体（CAR）T细胞、特异性抗原肽等新兴疗法结合，大大提高肿瘤免疫治疗的效率。MyD88的上述作用使其成为多种恶性肿瘤极具前景的诊疗靶点。摘 要：MyD88作为一种通用的信号衔接蛋白，调节大多数Toll样受体（TLR）和白细胞介素1受体（IL-1R）级联的信号传导，参与介导先天免疫，调节炎症微环境和肿瘤微环境。通过TLR/MyD88信号途径，MyD88直接或间接地影响多种下游的免疫因子分泌，诱导肿瘤细胞和/或免疫细胞分泌蛋白或表面分子改变，同时引起肿瘤组织局部免疫细胞种类、数量及功能的改变，导致炎症微环境恶化及肿瘤微环境重塑，最终引起肿瘤免疫耐受和免疫逃逸。MyD88在肿瘤免疫治疗中具有双重作用，一方面通过分泌免疫抑制因子，抑制疗效；另一方面将MyD88信号与嵌合抗原受体（CAR）T细胞、特异性抗原肽等新兴疗法结合，大大提高肿瘤免疫治疗的效率。MyD88的上述作用使其成为多种恶性肿瘤极具前景的诊疗靶点。     

NLRP3炎症小体在槲皮素诱导宫颈癌HeLa细胞凋亡中的作用

目的:探讨槲皮素对人宫颈癌HeLa细胞增殖及凋亡的影响,并探讨其可能的机制。方法:以不同浓度槲皮素（20、40和80 μmol/L）处理HeLa细胞36 h,用噻唑蓝（MTT）法检测细胞增殖情况,流式细胞实验检测细胞凋亡情况,Western blot和实时定量PCR法检测NLRP3炎症小体的表达情况。结果:槲皮素能使HeLa细胞活力降低,差异具有统计意义（P<0.05)。流式细胞结果表明不同浓度槲皮素组均可诱导HeLa细胞凋亡,且能抑制NLRP3炎症小体相关蛋白NLRP3、ASC及Caspase-1的表达。结论:槲皮素能通过下调HeLa细胞中NLRP3炎症小体的表达发挥其促癌细胞凋亡作用。     

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.     

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.     

Temozolomide treatment in glioma--experiences in two university hospitals in Finland

Thirty-two patients with relapsing glioma were treated with temozolomide in two university hospitals in Finland. One patient (3%) had complete response and 9 (28%) partial response, with 8 patients (25%) showing stable disease. Median progression-free survival for these 18 patients (56%) was 7 months (range 2-11+). The remaining either had progressive disease (25%) or only clinical evaluation (19%). Karnofsky score improved in 34% of patients and decreased in 3%. Symptoms were alleviated in 44% and deteriorated in 9%. Grade 3-4 toxicity was detected in 9% of the patients. Only 4% of the days in treatment were spent in hospital. An average 1.8 neuroradiological investigations, 6.9 laboratory visits, and 5.3 visits to the oncologist were made. This study confirms that temozolomide has positive effects on the outcome of often heavily pretreated glioma patients. High drug costs are compensated by prolonged home care and even the possibility to maintain working capacity.