乳腺癌发生过程中ER、PR、HER-2及WT1蛋白表达变化的研究

目的探讨雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体-2(HER-2)及Wilms瘤基因1(WT1)在乳腺癌发生过程中的表达变化。方法收集2011年1月至2011年12月95例经活检病理组织学检查确诊的乳腺疾病患者(乳腺导管上皮增生22例、乳腺导管上皮不典型增生23例、导管内癌23例及导管内癌微浸润27例),取组织病理切片后采用免疫组化SP法检测ER、PR、HER-2和WT1蛋白的表达水平,分别观察在导管上皮增生、不典型增生、导管内癌和导管内癌微浸润4种乳腺癌不同分期水平中的表达情况。结果ER、PR在各组中的阳性表达率无明显差异;HER-2在乳腺导管上皮增生、导管上皮不典型增生、导管内癌和导管内癌伴微浸润中的阳性表达率分别为0(0/22)、4.3%(1/23)、34.8%(8/23)和51.9%(14/27),其表达逐渐增加(P<0.001);WT1的阳性表达率分别为31.8%(7/22)、60.9%(14/23)、13.0%(3/23)和22.2%(6/27),在不典型增生患者中最高,差异有统计学意义(P=0.002)。在导管内癌的患者中,ER、PR的表达与否(+/﹣)和WT1阳性率呈一定的相关性,ER或PR阳性表达者其WT1阳性率更高(P<0.05)。结论ER、PR表达的逐渐增加可提示乳腺癌的发生发展,而HER-2在乳腺癌的启动中发挥重要作用,WT1不仅发挥了癌基因的功能,同时也可参与肿瘤的侵袭和转移,促进其演进过程。

Expression of BI-1 protein and its significance in breast cancer

Objective： To investigate the correlations of expression of Bax inhibitor-1 （BI-1） gene and the receptors of estrogen and progestogen in breast cancer and its significance. Methods： Immunohistochemical methods had been used to detect the expressions of BI-1 gene and receptors of estrogen and progestogen in breast cancer. Results： The positive rates of expressions of BI-1 gene, estrogen receptor （ER） and progestogen receptor （PR） in breast cancer were 77.08%, 60.42% and 54.17%, respectively. The positive rate of expression of BI-1 gene was higher in the group with negative expression of ER than the positive group, their positive rates were 76.92% and 52.27%, respectively; but there was no statistical difference between the two groups with positive and negative expressions of PR. The positive rate of expression of BI-1 gene was also higher in the group with positive lymph node metastasis than the non-lymph node metastasis group, and their positive rates were 64.58% and 36.36%, respectively. The difference was statistically significant （P 〈 0.05）. Conclusion： BI-1 gene, in combination with ER, has guiding significance for patients with breast cancer to choose individual chemotherapy and radiotherapy after operation and can become an important indicator for judging the prognosis of breast cancer.

肺癌肿瘤抑制因子1在雌激素受体、孕激素受体不同表达乳腺癌患者中的临床意义

目的分析肺癌肿瘤抑制因子1(tumor suppressor in lung cancer 1,TSLC1)与乳腺癌临床病理和预后关系。方法收集女性乳腺癌组织125例,采用免疫组织化学技术检测TSLC1表达。结果 TSLC1主要表达在乳腺癌细胞质,其阳性率为38.4%(48/125),与患者的年龄、肿瘤大小、淋巴结转移、临床分期、人类表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)表达无关,而与雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)表达相关(P<0.001)。ER^+(阳性)患者TSLC1阳性率低于ER-(阴性)患者[28.4%(25/88)与62.2%(23/37)];同样,PR^+患者TSLC1阳性率低于PR^-患者[24.3%(17/70)与56.4%(31/55)]。Z检验显示在ER^+PR^-的乳腺癌患者中TSLC1^-和TSLC1^+患者3年生存率差异有统计学意义(83.3%与14.3%,P=0.007),总体生存曲线差异有统计学意义(P=0.003)。Cox多因素回归分析,TSLC1不是ER^+PR^-乳腺癌患者独立的危险预后因素(比值比10.696,95%可信区间0.988~115.843,P=0.051)。结论 TSLC1在乳腺癌致病机制中与ER、PR相关,可作为临床ER^+PR^-乳腺癌患者新的预后指标。

Clinical signification of high-mobility group box 1protein(HMGB1) expression in infiltrating ductalcarcinoma breast tissue

Objective: Exploring the clinical signification of high-mobility group box 1 protein(HMGB1) expression in infiltrating ductal carcinoma(IDC) breast tissue. Methods: The expression of HMGB1 protein in IDC breast tissue was detected by immunohistochemistry, and the relations among size of tumour, lymph node metastasis, clinical staging, estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor 2(HER-2) were also analyzed. Results: Fortysix cases out of 60 cases of IDC breast tissue showed positive or strong positive HMGB1 expression(76.67%), statistical significance was observed between HMGB1 expression with clinical staging(P < 0.01), lymph node metastasis(P < 0.01), breast cancer ER(P < 0.05) and HER-2(P < 0.05), however same conclusion can not be drawn between HMGB1 with either size of tumour or PR expression(P > 0.05) in IDC breast tissue. Spearman analysis showed negative correlation between HMGB1 expression and ER, and positive correlation between HMGB1 expression and clinical staging, lymph node metastasis together with HER-2. Conclusion: It's promising that HMGB1 expression in IDC tissue can be one of biological indicators of poor prognosis.

凯里酸汤对大鼠非酒精性脂肪肝病作用的分子机制

目的探讨凯里酸汤对大鼠非酒精性脂肪肝病(NAFLD)作用的分子机制。方法结合文献数据库及TCMSP、PubChem、SEA、SwissTargetPrediction、SuperPred等数据库获取凯里酸汤的化合物成分及其潜在靶点,用Genecards及DisGeNet建立疾病靶点数据集,数据通过Venn制作工具、Cytoscape软件、蛋白质相互作用网络数据库(STRING)及注释、可视化和综合发现(DAVID)等数据库进行分析及网络可视化;18只大鼠均分为对照(ND)组(予正常饲料)、模型(HF)组(予高脂饲料)及凯里酸汤干预(HS)组(予高脂饲料加1 mL/100 g酸汤灌胃),连续12周,结束时麻醉处死各组大鼠,取心脏血及肝脏,采用生化分析仪检测各组大鼠血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、甘油三酯(TC)及总胆固醇(TG)水平,采用苏木精-伊红(HE)染色和油红O染色观察各组大鼠肝组织的形态学特征,采用实时荧光定量(RT-qPCR)、Western blot及免疫组织化学(IHC)染色检测各组大鼠肝组织中过氧化物酶增殖物激活受体α(PPARα)、雌激素磺基转移酶1E1(SULT1E1)及雌激素受体α(ERα)的表达。结果网络药理学方法获得凯里酸汤11个主要成分及PPARα、ERα等12个关键靶点,生物信息学分析显示凯里酸汤参与多个生物过程,并可能通过雌激素信号通路在NAFLD防治中起作用;RT-qPCR、Western blot及IHC结果显示,与ND组相比,HF组大鼠肝组织中SULT1E1表达增加(P<0.05),PPARα、ERα相对表达降低(P<0.05),HS组则相反(P<0.05)。结论凯里酸汤对大鼠NAFLD作用的分子机制可能与PPARα/SULT1E1/ERα/雌激素信号转导恢复有关。

ESR1 mutations:Piece de resistance

Estrogen and estrogen receptor-alpha(ER)signaling are important factors in the pathogenesis and treatment of ER-positive breast cancers.Therefore targeted therapies against ER,known as endocrine therapies,are widely used in the treatment of ER-positive breast cancers.While these therapies have shown great success,de novo and acquired resistance are common.The approach to the problem of endocrine therapy resistance is twofold:identify the mechanisms of resistance and develop alternative treatments to overcome these mechanisms.This review focuses on the progress and integration of these two aspects of resolving endocrine therapy resistance in ER-positive breast cancer patients.

雌、孕激素受体、生长激素受体、胰岛素样生长因子1受体与子宫内膜容受性的关系

辅助生殖技术(ART)经过近40年的发展,已取得突飞猛进的进展。但是临床妊娠率仍然徘徊在30%~40%。决定能否成功妊娠的因素主要包括2个方面,一是胚胎发育的质量,二是子宫内膜对胚胎的容受性。而在临床工作中,即使胚胎质量良好,种植率仍然不能令人满意。因此,如何提高子宫内膜容受性已经成为辅助生殖领域一个亟待解决的问题,了解影响子宫内膜容受性的相关因素,对于在种植窗期如何调节母体的内膜达到最佳的接纳胚胎的状态,具有重要的指导性意义。本文着重阐述子宫内膜容受性与雌激素受体(ER)、孕激素受体(PR)、胰岛素样生长因子1受体(IGF-1R)、生长激素受体(GHR)之间的关系,期望对临床判断子宫内膜容受性有所帮助。

G蛋白耦联雌激素受体-1与卵巢癌

G蛋白耦联雌激素受体-1(G protein-coupled estrogen receptor 1,GPER-1)是一种新型的雌激素受体,能够介导雌激素的快速非基因组效应。GPER-1与雌激素具有高亲和力,能与天然雌激素和人工合成雌激素结合,快速激活细胞内第二信使或级联信号通路,间接调节转录活动,从而介导雌激素的生物学效应。GPER-1的亚细胞定位存在争议,因其亚细胞定位可能取决于不同的细胞类型。另外,性别、年龄等内在因素以及细胞外刺激、损伤等外在因素也影响GPER-1在质膜的相对丰度。近年来研究表明GPER-1的表达与女性生殖系统肿瘤的发生、发展密切相关,在卵巢癌组织中高表达,参与卵巢癌的发生发展,并可能作为评价卵巢癌患者预后的指标,有望成为卵巢癌重要的治疗靶点。