雌激素受体α基因多态性与膀胱癌发病风险的相关性

目的  研究雌激素受体α基因单核苷酸多态性与膀胱癌易感性的关系。 方法  从两医院收集膀胱癌新发病例220例及同期健康体检对照220例,通过问卷收集研究对象一般情况,查阅电子病历收集临床检查资料;用多重高温连接酶检测反应技术（improved multiple ligase detection reaction,iMLDR）检测基因型;采用酶联免疫法检测两组血清中雌激素受体α（estrogen receptor alpha,ESRα）的表达量。 结果  病例组的体重指数、饮食及生活行为习惯和血红蛋白、中性粒细胞百分率等临床检查结果与对照组人群差异均有统计学意义（均有P < 0.05）。rs1801132位点基因及基因型频率与病理分级（χ²=9.607,P=0.022;χ²=24.468,P < 0.001）、远处转移（χ²=2.367,P=0.027;χ²=21.758,P=0.001）有关。膀胱癌患者血清中ESRα受体表达量低于正常人群（t=5.588,P < 0.001）。rs1801132位点多态性在不同基因型人群中膀胱癌发病风险均有统计学差异[GG：OR（95% CI）=0.325（0.141~0.751）,P=0.009;GC：OR（95% CI）=0.409（0.198~0.847）,P=0.016]。 结论  rs1801132位点多态性与膀胱癌发病相关,GG/GC基因型在膀胱癌中具有保护作用;rs2234693位点多态性与膀胱癌无相关性。     

ESRα和VDR基因多态性与乳腺癌易感性关系

目的探讨雌激素受体α(ESRα)、维生素D受体(VDR)基因多态性与乳腺癌发病风险关系。方法选取189例乳腺癌患者和374名非癌女性对照人群为研究对象,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和测序检测ESRα基因rs2234693和rs9340799位点、VDR基因rs10735810位点的多态性。结果ESRα基因rs9340799位点等位基因G在病例组的分布频率(15.08%)明显低于对照组(22.46%)(P=0.002),与等位基因A相比,经年龄校准的OR=0.580(95%CI=0.413~0.815);ESRα基因单体型CG在病例组的分布频率(13.7%)明显低于对照组(20.6%)(P=0.005),复合基因型CCGG在病例组的分布频率(1.59%)也明显低于对照组(5.61%)(P=0.025),其OR值分别为0.614(95%CI=0.436~0.864)和0.271(95%CI=0.080~0.921)。结论ESRα基因rs9340799位点多态性与乳腺癌发病紧密相关,携带有等位基因G,单体型CG或复合基因型CCGG的个体患乳腺癌的风险较低。     

雌激素受体亚型在多囊卵巢综合征发病中的作用

雌激素受体是核受体超家族成员之一,其有两种亚型:雌激素受体α和雌激素受体β.两种亚型在结构上有高度的同源性,但是组织分布和各组织成分中的表达明显不同,与配体结合后产生的生物效应也不同.二者表达及比例变化与组织的功能和病理变化有关.研究雌激素受体α和雌激素受体β的结构及其在女性生殖系统中的分布和功能,探讨其与多囊卵巢综合征的关系,对了解雌激素受体亚型的分布与功能的关系,以及分布的变异和异常调节与多囊卵巢综合征的关系都有重要意义.     

GC-MS法测定肉中雌激素残留量方法的研究

目的：建立GC-MS法测定肉中雌二醇、戊酸雌二醇、炔雌醚、苯甲酸雌二醇残留量的方法。方法：样品经乙腈超声萃取、离心,提取液经二氯甲烷反萃取、浓缩至干,残留物经交联葡聚糖LH-20柱净化后作TMS化反应,用GC-MS的SIM方法测定。结果：4种组分分离良好,并得到浓度与峰面积成正比的工作曲线,相关系数r〉0.997;其变异系数CV≤1.2%（n=6）,最低检出限≤20 ng/g,回收率范围为84.6%～92.4%。结论：该法具有灵敏、准确、精密、无杂质干扰等优点。     

Fetal growth restriction alters hippocampal 17-beta estradiol and estrogen receptor alpha levels in the newborn male rat

Fetal growth restriction (FGR) is associated with impaired neurodevelopmental outcomes in affected newborns. The pathogenesis of FGR-associated neurodevelopmental impairment implicates abnormal hippocampal function. The steroid hormone estrogen and its receptor, estrogen receptor alpha (ERα), are involved in the normal programming of hippocampal development and structure. However, the impact of FGR on hippocampal estrogen and hippocampal ERα is not well characterized. We hypothesized that FGR will reduce hippocampal and serum levels of 17-beta estradiol and its receptor, ERα, in the newborn rat hippocampus. We further hypothesize that FGR will reduce hippocampal ERα levels in a region-specific manner. To test our hypotheses, we used the well characterized rat model of FGR induced by uteroplacental-insufficiency in the pregnant Sprague-Dawley rat. Hippocampi and serum were obtained from FGR and control day 0 rat pups and examined for hippocampal 17-beta estradiol, serum 17-beta estradiol, and ERα mRNA and protein levels. Immunohistochemistry was performed to examine region-specific ERα staining. FGR decreased hippocampal 17-beta estradiol levels in the hippocampi of male newborn rats but not females. Serum 17-beta estradiol levels were not affected by FGR in either gender. FGR decreased hippocampal ERα mRNA levels in males but not females. Hippocampal ERα protein levels by Western blotting were not affected by FGR. However, FGR decreased apparent ERα staining in the cornu ammonis (CA)1, CA3, and dentate gyrus regions in the hippocampi of male newborn rats but not females. We conclude that FGR affects the programming of hippocampal estrogen and hippocampal ERα levels in the newborn rat in a gender-specific manner.     

Association of PvuII and XbaI polymorphisms in estrogen receptor alpha gene with the risk of hepatitis B virus infection in the Guangxi Zhuang population

Background and objectiveAvailable evidence has suggested that estrogen receptor alpha (ESR1) is implicated in the pathogenic process of hepatitis B infection. Therefore, we evaluated the association of PvuII (rs2234693) and XbaI (rs9340799) in ESR1 and HBV infection in Guangxi Zhuang populations.MethodsA total of 389 subjects were divided into four groups: 112 patients with chronic hepatitis B (CHB), 65 patients with hepatitis B virus (HBV)-related liver cirrhosis (LC), 107 patients with HBV-related hepatocellular carcinoma (HCC), and 105 healthy controls. The polymerase chain reaction–restriction fragment length polymorphism strategy was used to detect ESR1 gene PvuII and XbaI polymorphisms.ResultsCompared with healthy controls, binary logistic regression analyses show that the CC genotype of PvuII was associated with a significantly increased susceptibility to CHB compared with the TT genotype (OR = 1.760, 95% CI 1.316–2.831; p = 0.044). The PvuII CC genotype was also associated with significantly increased risk of HBV-related LC (OR = 1.921, 95% CI 1.342–2.478; p = 0.043). Similarly, the subjects bearing the homozygous CC genotype of PvuII polymorphism also had more than a 1.7-fold increased risk for development of HCC (OR = 1.748, 95% CI 1.313–2.787; p = 0.010) compared with those bearing the TT genotype. Furthermore, the AC haplotype was associated with a significantly increased risk of HCC with an OR of 1.456 (p = 0.003). In contrast, there were no significant differences in the genotype and allele of XbaI polymorphisms in the ESR1 gene between the groups of patients and healthy controls. In addition, ESR1 polymorphisms were not significantly associated with susceptibility to HBV-related HCC when using CHB and LC patients as references.ConclusionWe conclude that the CC genotype of PvuII in ESR1 is associated with an increased risk of CHB, HBV-related LC and HCC in Guangxi Zhuang populations.     

孕激素阻断子宫内膜癌前病变癌变雌孕激素受体的测定

目的 :孕激素治疗子宫内膜癌前病变 ,使其转变为正常内膜 ,测定治疗前后子宫内膜雌激素受体和孕激素受体 (ER.PR) ,以了解子宫内膜改变时 ,ER.PR的变化情况。方法 :对 32例癌前病变内膜孕激素治疗前后的石蜡切片 ,采用单克隆抗体免疫组化法测定子宫内膜 ER.PR。结果 :孕激素治疗后 ,子宫内膜由腺瘤样增生或非典型性增生逆转为正常内膜 ER.PR下降 ,前后有显著性差异 (P<0 .0 5 )。结论 :孕激素可有效的阻断子宫内膜癌前病变的恶变 ,并使其逆转为正常内膜 ,同时使子宫内膜 ER.PR下调。     

A case-control study of breast cancer stratified by estrogen receptor status

A population-based case-control study was conducted to examine whether tumor estrogen receptor status differentiated risk factor patterns for breast cancer. From December 1980 to December 1982, 458 women with newly diagnosed breast cancer and 568 control women, aged 20-54 years, from the Atlanta, Georgia, metropolitan area were interviewed. On the basis of tumor estrogen receptor results, cases were classified as receptor-positive or receptor-negative. Intercase analysis showed that age was positively and significantly associated with estrogen receptor-positive breast cancer (p = 0.001); the relative risk for an estrogen receptor-positive as opposed to an estrogen receptor-negative tumor was elevated threefold among women aged 50-54 years compared with those aged less than 35 years. In the case-control analysis, race was the only individual factor that demonstrated a significant difference in the risk for estrogen receptor-positive versus estrogen receptor-negative cancer (p less than 0.05), with blacks being at a 25% excess risk for estrogen receptor-negative cancer compared with whites. Although a history of benign breast disease was a risk factor for both positive and negative tumors, the association was stronger for the estrogen receptor-positive tumors. Postmenopausal women were at a lower risk for both cancer subtypes compared with premenopausal women. Compared with non-users, women who had ever taken oral contraceptives had a 16% decrease in the risk for receptor-positive cancer and a 22% increase in the risk for receptor-negative cancer. These results are consistent with the notion that certain exposure variables may relate to hormonal status, possibly by augmentation or suppression of estrogen receptor activity.     

Role flexibility among telemedicine service providers in the north-west and west of Ireland

A recent review of telemedicine services in the north-west and west of Ireland identified 11 telemedicine services, most of which were in the early stages of implementation. A qualitative approach was used to review them. Semistructured interviews were conducted with a multidisciplinary group of primary- and secondary-care providers (n = 21) who were involved with either synchronous or asynchronous telemedicine services. Data were analysed according to the principles of framework analysis. Participants described the ways in which they were flexible about their workload, professional identities and roles to facilitate the organization and delivery of telemedicine services, and to ensure that services ran smoothly. While the positive effect of product champions and members of a wider supportive network or alliance on the conception and development of telemedicine services must be acknowledged, questions remain about associated long-term implementation and sustainability.     

Role of coffee in modulation of diabetes risk

Coffee consumption has been associated with a lower risk of type 2 diabetes. This association does not depend on race, gender, geographic distribution of the study populations, or the type of coffee consumed (i.e., caffeinated or decaffeinated). This review discusses the strength of this relationship, examines the possibility that the pattern of coffee consumption could influence the association, and evaluates the possible relationship between coffee consumption and other risk factors associated with diabetes. Particular attention is paid to the identification, on the basis of the scientific evidence, of the possible mechanisms by which coffee components might affect diabetes development, especially in light of the paradoxical effect of caffeine on glucose metabolism. In addition to the role of coffee in reducing the risk of developing type 2 diabetes, the possible role of coffee in the course of the illness is explored. Finally, the possibility that coffee can also affect the risk of other forms of diabetes (e.g., type 1 diabetes and gestational diabetes) is examined.     

Breast cancer incidence in young women by estrogen receptor status and race.

A population-based study was utilized to calculate breast cancer incidence rates in White and Black women, ages 30 to 54, according to tumor estrogen receptor status. Both racial groups had higher incidence curves for estrogen receptor negative breast cancer between ages 30 and 49. There was an excess of receptor negative cancer in young Black women, an observation that may help explain the racial disparity in breast cancer survival.     

雌、孕激素受体在绝经期子宫全层中的表达

目的:通过研究绝经期雌、孕激素受体在子宫全层中的表达,比较它们在子宫内膜、浅肌层、深肌层和浆膜层中的梯度分布情况,为乳腺癌术后在去除子宫内膜的情况下可否安全地服用他莫昔芬寻找理论依据。方法:选择因子宫脱垂需行子宫全切术的绝经期患者,在相同的宫体部位分别取子宫体的全层组织,用免疫组织化学法研究不同病症中雌、孕激素受体在子宫全层(内膜层、浅肌层、深肌层及浆膜层)中的表达情况,采用LeicaQ500IW图像分析仪和Olympus光学显微镜进行测定,对雌、孕激素受体阳性细胞的表达率进行比较。结果:雌、孕激素受体在绝经期子宫内膜层中高度表达,与其他各层比较,差异有统计学意义(P=0.001);浆膜层含量最少,与其他各层比较,差异有统计学意义(P=0.000);浅肌层与深肌层之间比较,差异无统计学意义(P=0.148)。结论:绝经期雌、孕激素水平急剧下降,子宫各层中雌、孕激素受体含量较低,但在子宫内膜中仍占多数,故绝经期乳腺癌妇女长期服用他莫昔芬会引起子宫内膜病变,剥除子宫内膜后,破坏了大部分雌、孕激素受体,可以安全、有效地长期服用他莫昔芬。     

The role of estrogen receptor, vitamin D receptor and calcium receptor genotypes in the pathogenesis of colorectal cancer

In this study, the Xbal polymorphisms of the estrogen-, the Bsml polymorphism of the vitamin D- as well as the A986S polymorphism of the calcium-sensing receptor genes were investigated in 56 patients with colorectal cancer. The expression of erbB-2, epidermal growth factor receptor, ras, p53 and their relationship to estrogen-, vitamin D- and calcium-sensing receptor genotypes were also studied. In subjects exhibiting XX genotype of the estrogen receptor gene or bb genotype of the vitamin D receptor gene, erbB-2 expression was significantly lower compared to those with xx, Xx or BB, Bb (6/56 and 11/56 vs. 31/56 and 26/56; p = 0.0043 and 0.041). The presence of the XX alleles of estrogen receptor gene significantly correlated with the overexpression of the epidermal growth factor receptor expression in tumors, whereas in xx and Xx genotypes, significantly higher expression was seen (7/56 vs. 30/56; p = 0.049). Analyzing the combinations of the two gene allelic variants, we have found XXbb genotype to be associated with a significantly lower erbB-2 expression, compared to other combinations (Xxbb, XxBb, XXBb) (2/7 vs. 7/7, 4/5, 4/5; p = 0.0011). Patients with AA calcium-sensing receptor genotype were in higher UICC stages at the time of discovery of their disease than those with AS genotype. The AA allelic variant of the calcium-sensing gene was more frequent among patients with colorectal cancer compared to controls (36/56 vs. 36/112; p = 0.0004). Our observations raise the possibility that estrogen-, and vitamin D receptor gene polymorphisms accompanied with variable oncogene expression might influence the pathogenic processes resulting in the development of colorectal cancer. The A986S polymorphism of calcium-sensing receptor might also be a prognostic marker of the disease.     

GPR30在子宫内膜异位症发病机制中的研究进展

子宫内膜异位症的特征是子宫内膜样组织出现在子宫以外部位,其严重影响着患者的生活质量。尽管子宫内膜异位症病因和发病机制不清,但一般认为子宫基底层内膜异位于宫腔以外生长与高雌激素刺激密切相关,并涉及内膜细胞生理、生物化学和分子生物学等机制。 G蛋白耦联受体超家族成员－GPR30是新型雌激素膜受体。近年的基础研究发现其介导的快速效应途径致靶细胞增殖、侵润,在子宫内膜异位症发生发展中起重要作用。该文就近年对GPR30在子宫内膜异位症发病机制中的作用进行解读。     

雌孕激素受体在上皮性卵巢肿瘤中的表达和意义

目的:分析雌、孕激素受体(ER、PR)在上皮性卵巢肿瘤中的表达情况,探讨其与上皮性卵巢肿瘤发生、发展的关系,明确ER、PR在上皮性良、恶性卵巢肿瘤以及上皮性卵巢恶性肿瘤中不同的临床分期、病理分级、病理类型中的表达,从而对上皮性卵巢肿瘤的诊断、内分泌及基因治疗提供依据,以利于制定个体化的治疗方案。方法:对60例上皮性卵巢肿瘤患者病理切片采用免疫组化SP法测定ER、PR;采用SPSS软件χ2检验、四格表确切概率法进行统计学处理。结果:①在上皮性卵巢良性肿瘤(22例)中ER阳性率27.27,PR阳性率22.72,阳性率较低;在上皮性卵巢恶性肿瘤(38例)中的阳性率较高(ER76.32、PR71.05),两者比较,χ2=13.79、χ2=13.07,P<0.01,均有显著性差异。②在上皮性卵巢恶性肿瘤中不同临床分期ER、PR的表达不同,随着临床期别的上升ER、PR的阳性率呈下降趋势。早(Ⅰ、Ⅱ)、晚(Ⅲ、Ⅳ)期比较,四格表确切概率法P>0.05,无显著性差异。③在上皮性卵巢恶性肿瘤中ER、PR在不同的病理分级中的阳性表达率不同,在高分化组的阳性率最高,在低分化组阳性率最低,P>0.05,无统计学意义。④在上皮性卵巢恶性肿瘤中不同病理类型的ER、PR表达不同,浆液性(21例)与粘液性(15例)肿瘤均呈高表达,但无显著性差异,P>0.05。结论:①ER、PR的阳性表达在上皮性卵巢良、恶性肿瘤之间有显著性差异。在上皮性良性肿瘤中呈低表达,而在上皮性恶性肿瘤中呈高表达。②ER、PR阳性表达在上皮性卵巢恶性肿瘤不同的临床分期、病理分级、病理类型中的表达不同,但无显著性差异。③临床工作中通过对它们的评价制定个体化治疗方案,指导治疗、判断预后。     

OTR、ER在子宫腺肌病中的表达及与痛经的关系

目的:探讨OTR、ER在子宫腺肌病患者在位及病灶组织中的表达及其与痛经的关系。方法:采用免疫组化法检测30例子宫腺肌病在位和异位内膜中OTR、ER的表达,以子宫正常肌层组织和在位内膜为对照。结果:在子宫腺肌病灶组织中OTR、ER的表达高于在位内膜组及对照组(P<0.05);在子宫腺肌病组的在位内膜和病灶组织中,痛经组OTR、ER的表达高于无痛经组及对照组(P<0.05);在不同痛经程度分组中OTR、ER的表达依次降低。在子宫腺肌病的在位内膜和病灶组织中,OTR、ER两者之间存在正相关关系。结论:子宫腺肌病组织中OTR、ER的表达随痛经程度增强而增加,在子宫腺肌病痛经的发生与发展间可能存在协同作用。     

绝经后妇女雌激素受体PvuⅡ基因多态性的研究

目的 了解甘肃省嘉峪关地区绝经后妇女雌激素受体基因多态性与绝经年龄及绝经相关症状发生情况的关系.方法 检测200例绝经后妇女雌激素受体PvuⅡ的等位基因及基因型频率分布的差异,同时进行绝经相关症状调查.结果 ①ER基因PvuⅡ酶切位点3种基因型间平均绝经年龄有显著差异(F=7.436,P<0.05);绝经前月经紊乱者绝经相关症状的发生率高(OR=3.214,P<0.05);绝经前月经紊乱及绝经前中出现大的生活事件者精神症状的发生率高(F值分别为6.345和4.214,均P<0.05).结论 ①绝经年龄受遗传因素的影响;②ER基因PvuⅡ酶切位点与绝经相关症状的出现相关;③社会环境和生活方式等多种因素参与了绝经的发生和绝经相关症状的出现.     

Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities, and modulation of cell proliferation by dinaphthofurans

A group of heterocyclic aromatic compounds, dinaphthofurans (DNFs), recently have been identified as potentially significant contaminants in freshwater sediments. In the present study, a battery of in vitro assays was used for detection of toxic effects of DNFs that are potentially associated with endocrine disruption and tumor promotion. Dinaphthofurans were found to act as relatively potent inducers of aryl hydrocarbon receptor (AhR)-mediated activity in the chemical-activated luciferase reporter gene expression DR-CALUX assay. The relative AhR-inducing potencies of DNFs were similar or even higher than relative potencies of unsubstituted polycyclic aromatic hydrocarbons (PAHs), with dinaphtho[1,2-b;2'3'-d]furan being the most potent AhR agonist. Two compounds, dinaphtho[2,1-b;2'3'-d]furan and dinaphtho[1,2-b;1'2'-d]furan, induced estrogen receptor (ER)-mediated activity in the estrogen receptor-mediated CALUX (the ER-CALUX) assay. Two types of potential tumor-promoting effects of DNFs were investigated, using in vitro bioassays for detection of inhibition of gap-junctional intercellular communication and detection of a release from contact inhibition. Although the acute inhibition of gap-junctional intercellular communication was not observed, all six tested DNFs were able to release rat liver epithelial WB-F344 cells from contact inhibition at concentrations as low as 100 nM. In summary, the present study indicated that DNFs can exert multiple biological effects in vitro, including induction of the AhR-mediated activity, release of cells from contact inhibition, and induction of ER-mediated activity.