Glutathione-S-transferases M1 (GSTM1) and GSTT1 genotype,smoking, consumption of alcohol and tea and risk of esophageal and stomach cancers: a case-control study of a high-incidence area in Jiangsu Province,China

To evaluate interactions between lifestyle factors and glutathione-S-transferases M1 (GSTM1) and GSTT1 genotypes with reference to development of esophageal and stomach cancers, we conducted a case-control study of 141 cases of esophageal cancer, 153 cases of stomach cancer and 223 population-based controls in Huaian City of Jiangsu Province, China. GSTM1 and GSTT1 genotypes were identified by multiplex polymerase chain reaction. The GSTM1 null genotype was associated with an increased odds ratio for esophageal cancer (2.17, 95% confidence interval=1.35-3.50), but not for stomach cancer. A combined effect was also observed between smoking and the GSTM1 null genotype with regard to esophageal risk. Tea drinking was a protective factor for both cancers, its effect being independent of the GSTT1 and GSTM1 genotypes. These findings suggest the GSTM1 polymorphism is involved in the susceptibility to esophageal cancer development, and tea consumption reduces the risk of esophageal and stomach cancers.     

Annexin-1与BFGF在精原细胞癌中表达及临床意义

目的:研究膜联蛋白-1(Annexin-1)与BFGF在精原细胞癌组织中的表达情况,探讨其临床意义。方法:应用免疫组织化学SABC法检测25例精原细胞癌组织,25例正常睾丸组织中膜联蛋白-1与BFGF的表达情况,并对膜联蛋白-1与精原细胞癌的关系进行分析。结果:正常睾丸组织及精原细胞癌中膜联蛋白-1与BFGF阳性率分别为76.00%、16.00%和20.00%、88.00%。膜联蛋白-1的表达与肿瘤的临床分期和肿瘤分化程度无关(P>0.05)。结论:联合检测Annexin-1、BFGF有助于提高精原细胞癌的早期诊断率。     

大肠癌患者血清中巨噬细胞抑制因子-1升高的临床价值研究

目的 探讨巨噬细胞抑制因子1(MIC-1)在大肠癌诊断和早期诊断、治疗监测及复发预警中的临床价值.方法 应用自主研制的MIC-1检测试剂盒检测239例不同临床分期的大肠癌患者、16例肠道良性疾病患者及200例健康人血清样本中MIC-1水平,并对部分肿瘤患者进行连续监测;应用罗氏Cobas 601电化学发光免疫分析仪检测...     

Wnt/β-catenin信号通路在阿尔茨海默病神经元变性中的研究进展

目的：阿尔茨海默病(Alzheimer’s disease,AD)是目前老年人最常见的痴呆类型,由于AD发病机制复杂,迄今尚未完全阐明。AD最重要的神经病理学特征是β淀粉样蛋白（amyloid-beta eptide, Aβ）沉积、Tau蛋白过度磷酸化形成神经纤维缠结以及脑内神经炎症反应的激活,并伴随着神经元的损伤及学习记忆功能受损。越来越多的研究指出Wnt/β-连环蛋白（Wnt/β-catenin）信号通路在神经退行性疾病中,尤其是AD中发挥了重要作用。为明确Wnt/β-catenin信号通路与AD发病、Aβ沉积、Tau 蛋白和神经炎症的相关性及其机制,对相关文献进行综述。方法：选择Wnt/β-catenin信号通路与AD、Aβ神经毒性、Tau 蛋白磷酸化及神经炎症相关的国内外相关文献进行综述。结果：研究表明Wnt/β-catenin信号通路参与AD的发生和发展,当该通路激活时可以抑制Aβ的沉积、Tau的过度磷酸化及神经炎症,反之则促进Aβ的产生、聚集以及Tau蛋白的磷酸化,神经炎症的发生。结论：本文就Wnt/β-catenin信号途径在AD发病中的重要性加以概述,为AD机制的研究提供了理论基础,也提示激活Wnt信号传导途径可以作为治疗AD的潜在治疗靶点。dismutase,SOD）、丙二醛（malondialdehyde,MDA）和过氧化氢酶（catalase,CAT）水平采用试剂盒检测。qPCR和Western blot检测血浆Klotho的表达。Klotho表达量与氧化应激的相关性采用Pearson相关性分析。甲基化特异性PCR（MS-PCR）检测Klotho甲基化水平。CpG岛甲基化率采用焦磷酸盐测序法。结果：相对于对照组[（94.56±16.40） mU/L],观察组SOD含量[（79.86±18.24） mU/L]明显降低（t=4.487,P=0.000）,观察组MDA水平[（2.87±2.26） pg/mL]与对照组[（2.52±1.06） pg/mL]无统计学差异（t=1.675,P=0.097）,观察组CAT水平[（18.50±4.62） U/mg]与对照组[（25.26±3.54） U/mg]相比明显降低（t=8.605,P=0.000）。观察组（0.66±0.16）比对照组（1.04±0.10）血浆Klotho基因（t=14.93,P=0.000）降低;观察组（0.70±0.20）比对照组（1.04±0.10）血浆Klotho蛋白表达（t=10.92,P=0.000）降低,且Klotho蛋白表达量与SOD水平（r=0.768,P=0.000）和CAT水平（r=0.708,P=0.000）呈正相关。观察组Klotho启动子CpG岛甲基化水平升高。结论：Klotho甲基化可能是NSCLC患者血浆氧化应激状态的一个临床标志物。     

Plasma miR‐122 and miR‐200 family are prognostic markers in colorectal cancer

Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I‐IV disease from a population‐based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards. Plasma samples of non‐metastatic and metastatic colon cancer patients, each group consisting of ten patients with ‘good’ and ten patients with ‘bad’ prognosis were screened. Identified candidate miRNAs were further validated by RT‐qPCR in the whole study cohort. The association of the miRNA levels with patients' survival and the prognostic subtypes was analyzed with uni‐ and multivariate logistic regression and Cox proportional hazards regression models. Increased miR‐122 levels were associated with a ‘bad’ prognostic subtype in metastatic CRC (Odds ratio: 1.563, 95% confidence interval (CI): 1.038‐2.347) and a shorter relapse‐free survival and overall survival for non‐metastatic (Hazard ratio (HR): 1.370, 95% CI: 1.028‐1.825; HR: 1.353, 95% CI: 1.002‐1.828) and metastatic (HR: 1.264, 95% CI: 1.050‐1.520; HR: 1.292, 95% CI: 1.078‐1.548) CRC patients. Additionally, several members of the miR‐200 family showed associations with patients' prognosis and correlations to clinicopathological characteristics. The here identified miRNA markers, miR‐122 and the miR‐200 family members, could be of use in the development of a multi‐marker blood test for CRC prognosis.     

Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis

2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite of 17beta-estradiol, is known to induce mitochondria-mediated apoptosis through several mechanisms. We sought to study the effect of mitochondrialy targeted hOGG1 (MTS-hOGG1) on HeLa cells exposed to 2-ME. MTS-hOGG1-expressing cells exposed to 2-ME showed increased cellular survival and had significantly less G(2)/M cell cycle arrest compared to vector-only-transfected cells. In addition, 2-ME exposure resulted in an increase in mitochondrial membrane potential, increased apoptosis, accompanied by higher activation of caspase-3, -9, cleavage of Bid to tBid and protein poly(ADP-ribose) polymerase (PARP) cleavage in HeLa cells lacking MTS-hOGG1. Fas inhibitors cerulenin or C75 inhibited 2-ME-induced caspase activation, PARP cleavage, apoptosis and reversed mitochondrial membrane hyperpolarization, thereby recapitulating the increased expression of MTS-hOGG1. Hence, MTS-hOGG1 plays an important protective role against 2-ME-mediated mitochondrial damage by blocking apoptosis induced through the Fas pathway.     

乳腺癌新辅助化疗的乳房肿物体表定位膜定位

目的探讨乳房肿物体表定位膜（简称乳房尺膜）标记法在乳腺癌新辅助化疗中乳腺肿瘤病灶定位的应用价值。方法对120例乳腺癌患者新辅助化疗前同时采用乳房尺膜对乳腺肿瘤病灶的位置和边界进行标记。对于非隆起性乳腺肿瘤病灶,将尺膜直接贴在乳房上,正向标记;对于边界不清楚的肿瘤病灶在超声引导下确定边界。对于隆起性乳腺肿瘤病灶,尺膜贴在肿瘤病灶以外的正常乳房皮肤上,反向标记。应用TEC方案2个疗程后再次标记,结合超声、钼靶及核磁共振结果综合判断临床疗效,决定手术或改为TP方案继续化疗。术前复位第一次标记结果,按标记的乳腺肿瘤病灶的位置和边界手术。结果完全缓解26例,部分缓解76例,稳定10例,进展8例。其中,完全缓解的24例按尺膜标记的肿瘤病灶位置和边界行保乳手术,部分缓解的18例按尺膜标记的肿瘤病灶位置及残余肿瘤病灶边界外1．5～2．0cm行保乳手术;其余78例,按尺膜标记的肿瘤病灶边界,行简化根治术,其中局部晚期皮缘不充足的13例,采用腹部全厚游离皮瓣覆盖创面。结论乳腺癌新辅助化疗的肿瘤病灶定位应用乳房尺膜法准确且无创,有效节省了肿瘤病灶周围正常的乳腺组织及皮肤,患者依从性好,明显优于传统的坐标法、体表纹身法以及金属标志物法。乳房尺膜标记法操作简单,尺膜价格低廉,便于普及和推广。     

hsa-miR-19a-3p下调靶基因SEMA4C抑制胃癌细胞增殖、侵袭能力

目的:探讨SEMA4C在胃癌中的表达以及hsa-miR-19a-3p下调SEMA4C对胃癌细胞增殖、侵袭能力的影响.方法:收集23例胃癌组织和对应癌旁组织标本,采用免疫组化染色、Real-time PCR方法检测SEMA4C的表达,并分析其与临床资料的相关性;检索Targetscan、Miranda等数据库预测调控SEMA4C基因的microRNA,并利用Real-time PCR、双荧光素酶报告系统检测加以证实;通过脂质体转染使人胃癌细胞系BGC823内过表达hsa-miR-19a-3p,Real-time PCR、Western blot检测SEMA4C的表达,通过细胞集落形成实验和Transwell小室研究BGC823细胞的增殖、侵袭能力的变化.结果:胃癌组织中SEMA4C阳性率87.0%,高于癌旁组织(x2=20.30,P<0.000 1),胃癌组织中SEMA4C mRNA的表达高于癌旁组织(t=13.47,P<0.000 1).SEMA4C的表达与胃癌TNM分期(P=0.036 4)、分化程度(P=0.042 7)、淋巴结转移度(P=0.012 8)有关.生物信息学分析hsa-miR-19a-3p、hsa-miR-214-5p、hsa-miR-138-5p可能调控SEMA4C表达,胃癌组织中hsa-miR-19a-3p的表达低于癌旁组织(t=8.233,P<0.000 1),hsa-miR-214-5p(t=0.846 3,P=0.097 6)、hsa-miR-138-5p(t=1.345,P=0.185 7)表达与癌旁组织无明显差异,hsa-miR-19a-3p转染后荧光素酶表达下降至0.46±0.12(F=5.685,P=0.003 2).hsa-miR-19a-3p转染后,SEMA4C mRNA(F=34.39,P<0.000 1)、SEMA4C蛋白(F=67.49,P<0.000 1)表达减少,BGC823细胞克隆数目减少(F=20.77,P<0.000 1),Transwell下室细胞数较少(F=16.37,P=0.000 4).结论:SEMA4C在胃癌中过表达并与肿瘤的发生发展有关,hsa-miR-19a-3p通过下调靶基因SEMA4C抑制胃癌细胞增殖、侵袭能力来发挥其抗肿瘤效应.