T-cell immunoglobulin mucin molecule-3, transformation growth factor β, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma

BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) have not been elucidated.AIM To examine the correlation between Tim-3,TGF-β and CXCL12 expression and DLBCL prognosis.METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups,respectively.The expression of Tim-3,TGF-β,and CXCL12 was detected immunohistochemically.Patients were followed up for 3 years,and progression-free survival was recorded.Cox mult-ifactorial analysis was performed to analyze the risk factors for poor prognosis.RESULTS The positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in DLBCL tissues than in non-cancerous(control) tissues(P < 0.05).One-year postsurgery,the positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment(P < 0.05).The 3-year progression-free survival of 97 patients with DLBCL was 67.01%(65/97).Univariate analysis revealed that clinical stage,bone marrow infiltration,International Prognostic Index(IPI) score,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were associated with poor prognosis(P < 0.05).Multivariate Cox regression analysis demonstrated that clinical stage Ⅲ–Ⅳ,bone marrow infiltration,mediate-to-high-risk IPI scores,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were independent risk factors affecting prognosis(P < 0.05).CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3,TGF-β,and CXCL12,and a high expression of all three indicates a poor prognosis.

Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease

Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.

T细胞因子3在非小细胞肺癌中的表达

目的研究T细胞因子3(T cell factor 3,TCF-3)在非小细胞肺癌中的表达及分布情况。方法采用50对人非小细胞肺癌组织标本及其正常癌旁组织对照,进行免疫组化检测TCF-3蛋白在肺癌组织及正常肺组织中的表达及分布情况;采用5种人非小细胞肺癌细胞系及2种正常人支气管上皮细胞系进行实时荧光定量PCR,Western blot检测肺癌细胞系中TCF-3在mRNA和蛋白水平的表达情况。结果 (1)TCF-3在肺癌组织中表达,表达率为48%(24/50),在正常肺组织中未见表达。TCF-3在肺癌细胞胞核与胞质同表达,以细胞核表达为主。(2)TCF-3在A549、H520、HBE、BEP-2D 4种细胞系中mRNA及蛋白水平均有表达。结论 TCF-3在肺癌组织及细胞系中均表达,TCF-3蛋白在细胞核与细胞质同表达,但以细胞核表达为主。

凋亡相关蛋白3及活化T细胞核因子3在卵巢上皮性肿瘤组织中的表达及与临床病理特征相关性研究

目的 探讨凋亡相关蛋白3（Apoptosis associated protein 3,APR3）及活化T细胞核因子3（Nuclear factor of activated T-cell,NFAT3）在卵巢上皮性肿瘤组织中的表达及与临床病理特征的相关性.方法 收集2014年4月至2015年4月住院治疗的92例卵巢上皮性肿瘤患者,其中恶性肿瘤患者23例,交界性肿瘤患者24例,良性肿瘤患者45例,采用免疫组化方法检测所有人组患者肿瘤组织中APR3和NFAT3表达,比较不同类型卵巢上皮性肿瘤的APR3和CaN-NFAT3的表达差异,分析恶性卵巢上皮性肿瘤患者APR3和NFAT3的表达与临床病理因素的相关性,分析恶性卵巢上皮性肿瘤患者APR3和NFAT3的表达相关性.结果 恶性卵巢上皮性肿瘤APR3阳性表达率（78.26％）明显高于交界性肿瘤（41.67％）和良性肿瘤（22.22％）,差异均有统计学意义（χ^2=5.864、7.632,均P〈0.05）;恶性卵巢上皮性肿瘤APR3表达与组织分化程度、临床分期、腹腔脏器和淋巴转移及腹水均明显相关（χ^2=7.425、7.262、8.421、5.031,均P〈0.05）.恶性卵巢上皮性肿瘤NFAT3阳性表达率（56.52％）明显高于交界性肿瘤（29.17％）和良性肿瘤（17.78％）,差异均有统计学意义（χ^2=6.829、7.547,均P〈0.05）;恶性卵巢上皮性肿瘤NFAT3表达与组织分化程度、临床分期及腹腔脏器和淋巴结转移均明显相关（χ^2=5.253、6.367、8.021,均P〈0.05）.恶性卵巢上皮性肿瘤患者APR3的表达与NFAT3的表达呈正相关（r=0.032,P〈0.05）.结论 APR3和NFAT3在恶性卵巢上皮性肿瘤中的表达明显增加,与患者组织分化程度、临床分期、腹腔脏器和淋巴转移密切相关,且两者表达呈明显正相关,可能与恶性卵巢上皮性肿瘤发生和发展有关.

Eps15同源结构域包含蛋白2通过调控Cyclin D1-CDK4-pRb信号轴影响食管鳞癌细胞的增殖

微丝结合蛋白是微丝细胞骨架的重要组成成分,它们通过促进微丝的聚合和解聚来影响微丝的动力学。大量研究已经表明,微丝和微丝结合蛋白参与细胞癌变的所有阶段。我们通过对食管癌蛋白质组数据挖掘结果显示,微丝结合蛋白Eps15同源结构域包含蛋白2(EHD2)在食管癌组织中低表达,且EHD2低表达的食管癌患者预后不良。以往的研究已经证明,EHD2参与调控糖代谢、自噬和肿瘤迁移。然而,EHD2在食管癌进展中的作用和机制仍不清楚。本研究旨在探究EHD2在食管鳞癌细胞中的影响及其作用机制。免疫荧光和细胞组分分离结果显示,EHD2不仅定位于细胞膜和细胞质,还存在于细胞核中。使用克隆形成实验、EdU细胞增殖实验和细胞流式术检测EHD2对食管鳞癌细胞增殖能力的影响。结果显示,过表达EHD2和EHD2-3×NLS(核定位信号)抑制食管鳞癌细胞增殖和细胞周期G_(1)/S转换;同时,双荧光素报告基因结果显示,过表达EHD2和EHD2-3×NLS抑制Wnt信号通路活性。而siRNA敲降则获得相反的结果。免疫共沉淀和Duolink-PLA实验证明,EHD2与Wnt信号通路关键分子β-连环蛋白(β-catenin)和T细胞因子3(T-cell factor 3,TCF3)相互作用。蛋白质印迹和荧光定量PCR结果证实,过表达EHD2和EHD2-3×NLS抑制TCF3下游与增殖和细胞周期相关的靶基因的转录,以及细胞周期蛋白D1(cyclin D1)、细胞周期蛋白激酶4(CDK4)和pRb的蛋白质表达。以上结果表明,核EHD2与β-catenin和TCF3复合体相互作用,通过Cyclin D1-CDK4-pRb信号轴来调控食管鳞癌细胞的增殖和细胞周期进程。