大豆异黄酮的选择性雌激素受体调节剂作用

近年来 ,选择性雌激素受体调节剂和大豆异黄酮的研究不断深入 ,逐步证实大豆异黄酮在不同组织可以表现为雌激素激动剂和 (或 )拮抗剂的作用 ,本文将对大豆异黄酮的选择性雌激素受体调节剂的作用、作用机理以及应用和发展前景等进行概述。     

选择性雌激素受体调节剂及其心血管保护作用

选择性雌激素受体调节剂 (SERMs)是一类在不同靶组织中可表现为雌激素激动剂或拮抗剂作用的化合物。雷洛昔芬是新一代SERMs代表药物。SERMs作用机制涉及雌激素受体、配体、应答元件、雌激素受体相关蛋白等方面。SERMs对于心血管疾病保护作用主要表现在对血脂的调节和对血管壁的直接作用。与激素替代疗法比较 ,SERMs对不同脂蛋白调节作用各异 ;SERMs具有调节血管壁增殖作用 ,其机制可能与eNOS(内皮一氧化氮合酶 )激活、Akt和ERK信号转导途径有关     

雌激素及雌激素受体对高血压心肌肥厚的影响

雌激素通过雌激素受体（estrogen receptor,ER）的介导对心血管系统发挥保护作用。雌激素被动扩散进入细胞后与雌激素受体结合,通过影响肾素血管紧张素系统（RAS）、NO合成、钙离子通道,改善脂质代谢等方面导致高血压心肌肥厚。雌激素受体调节剂（SERMs）如雷洛昔芬等也可以与ER结合,发挥抗心肌肥厚的作用。     

雌激素及其受体与自身免疫性疾病

自身免疫性疾病有明显的性别差异，女性的发病率显著高于男性，表明雌激素影响这类疾病的发生。雌激素及其代谢产物水平、雌激素受体基因多态性、雌激素受体介导的信号通路等方面与自身免疫性疾病密切相关，雌激素及其受体在自身免疫性疾病治疗中发挥重要作用。     

103例乳腺癌组织学与雌激素受体的研究

应用生物素抗生物素过氧化酶法对103例乳腺癌石蜡切片进行雌激素受体检测,结果发现雌激素受体阳性率在导管内癌中较高,占71%,而在浸润性导管癌、髓样癌中较低,分别占57%、29%。分析了雌激素受体和组织类型关系,探讨了它和组织分级及核分级之间的联系。雌激素受体阳性率随组织分级升高而降低,随核的分级升高而增加。说明乳腺癌组织分化好,雌激素受体表达倾向阳性,而分化低的肿瘤,雌激素受体表达倾向阴性。雌激素受体阳性患者比阴性患者复发率低,存活时间长,预后好,其检测有助于判断患者预后,安排合理的治疗方案,提高治愈率。     

雌激素、雌激素受体与膀胱癌间关系的研究进展

目的:探讨雌激素与雌激素受体对膀胱癌发生、发展的影响,为膀胱癌的内分泌治疗提供新的思路.方法:查阅近年来国内外膀胱癌与雌激素、雌激素受体间关系的相关文献,对其进行研究总结.结果:膀胱癌的病因、发病机理、复发机理还不十分明确,治疗方法也不完善.雌激素、雌激素受体可能对膀胱癌的发生发展有一定作用.结论:研究雌激素、雌激素受体与膀胱癌发生、发展的关系,对膀胱癌的诊断与治疗方面有重要意义.     

雌激素受体(ESR)基因多态性与疾病相关性的研究进展

雌激素受体是一种受配体激活的转录因子,由配体结合区、DNA结合区、转录激活区组成.雌激素受体对于对雌激素敏感的组织是一个重要的调节元件,如子宫内膜、乳腺、骨组织、肝脏等.雌激素的功能是刺激组织的增殖、分化,因此受体功能的变化可能有重要的临床意义.雌激素受体基因的多态性,单倍构型与它的生物学功能是相关的,研究认为ESR基因多态性与乳腺癌、骨质疏松症、HBV感染、子宫内膜异位症、冠心病等疾病存在相关性.该研究从雌激素受体的结构、功能与疾病的相关性方面作一综述.     

雌激素营养和保护神经元的作用机制

雌激素与神经营养因子一样,在促进神经元的分化和存活,保护神经元,维持正常的功能等方面有重要作用.雌激素替代治疗能保护胆碱能神经元,改善认知功能和记忆,但对其作用的机理尚未完全了解.一般认为通过神经营养因子及其受体的相互调节,作用于相应的信号转导途径.     

ER、PR及其相应拮抗剂与甲状腺癌的相关性研究进展

雌激素受体(ER)、孕激素受体(PR)在甲状腺癌中的异常表达说明性激素受体在甲状腺癌的发病机制中起重要作用.ER、PR通过经典的基因途径及非基因途径对甲状腺癌的发生、发展及生物学特征产生重要影响.性激素受体拮抗剂抑制甲状腺癌细胞增殖作用的研究,将为甲状腺癌的治疗提供新的选择方案.     

高效液相色谱法测定的雌激素受体临床应用于人乳腺癌

应用体积排阻高效液相色谱法(SEHPLC)分析13例人乳腺癌组织的雌激素受体。此法能迅速检出雌激素受体的8S及4S亚单位,为选择对内分泌治疗敏感的乳腺癌病人提供了新的依据。     

Histological and immunohistochemical study of estrogen and progesterone receptors in normal human breast tissue in adult age groups vulnerable to malignancy

Analysis of receptor status has become standard procedure for assessing breast cancer patients. Estrogen causes epithelial proliferation in breast tissue via the estrogen receptor (ER). The progesterone receptor (PR) is also regulated by the estrogen gene. Analyzing ER and PR together gives information regarding the likely response of carcinoma patients to hormonal therapy. The aim of the present study was to record the expression patterns of ER and PR in normal mammary tissue in different age groups to provide reference data to facilitate histological diagnosis. Breast tissues from the upper outer quadrant of each side of 27 adult female cadavers were examined after H & E staining. ER and PR were identified and examined by immunohistochemistry. The percentage area occupied by parenchyma relative to stromal tissue was calculated in different age groups and was about 4:6, 3.5:6.5, 3:7, 2:8, and 1.5:8.5 in the 3rd, 4th and 5th, 6th, 7th, 8th and 9th, and 10th decades of life, respectively. Both ER and PR were present in all age groups and the numbers of both receptors were maximal during the 4th decade. The distribution and staining patterns for both ER and PR were recorded in different age groups. The contiguous pattern of ER, which is considered pathognomonic of breast carcinoma, was not seen except in one case in the 6th decade. Moderately stained ER and PR receptor sites predominated throughout. The study of normal breast tissue of similar age might provide comparisons that will help histopathologists to make clinical diagnoses from breast biopsies. Clin. Anat. 29:729–737, 2016. © 2016 Wiley Periodicals, Inc.     

雌激素受体α 共激活子与乳腺癌

在乳腺癌发生发展过程中,雌激素受体（estrogen receptor α ,ERα）信号途径的活性增强,一个重要的原因是ERα共调节因子的变化。ERα共调节因子可分为共激活子和共抑制子。本文对ERα共激活子的种类、与ERα的结合方式、作用机制及其与乳腺癌的关系进行了综述。     

Association of three single nucleotide polymorphisms of ESR1 with breast cancer susceptibility: a meta-analysis

Expression of estrogen receptors is correlated with breast cancer risk, but inconsistent results have been reported. To clarify potential estrogen receptor (ESR)-related breast cancer risk, we analyzed genetic variants of ESR1 in association with breast cancer susceptibility. We performed a meta-analysis to investigate the association between rs2234693, rs1801132, and rs2046210 (single nucleotide polymorphisms of ESR1), and breast cancer risk. Our analysis included 44 case-control studies. For rs2234693, the CC genotype had a higher risk of breast cancer compared to the TT or CT genotype. For rs2046210, the AA, GA, or GA + GG genotype had a much higher risk compared to the GG genotype. No significant association was found for the rs1801132 polymorphism with breast cancer risk. This meta-analysis demonstrates association between the rs2234693 and rs2046210 polymorphisms of ESR1 and breast cancer risk. The correlation strength between rs2234693 and breast cancer susceptibility differs in subgroup assessment by ethnicity.     

Assessment of hormone receptor status in breast cancer

The aim of the present paper was to investigate the most adequate method for the assessment of hormone receptor status in breast cancer in routine clinical settings. Subjects were 486 patients with primary breast cancer who underwent surgery and postoperative tamoxifen monotherapy in 1982-1993. Using representative sections of the primary lesion in each patient, estrogen receptors (ER) were immunohistochemically stained. Patients were divided into ER-positive and ER-negative groups using various methods, and then overall and 5 year recurrence-free survival rates were compared. The results of ER status, which are diagnosed on entire cancer area and invasive cancer area, matched in 98% of cases. When assessing prognosis based on the proportion of positive cells, a significant difference in 5 year recurrence-free survival was seen between ER-positive and ER-negative patients for a cut-off of 10%, and in overall and 5 year survival for a cut-off of 33%. Based on the proportion and the intensity of positive cells (Allred score), a significant difference was seen in overall and 5 year survival for a cut-off in total scores between 4 and 5 points. When assessing hormone receptors of breast cancer in routine clinical settings, it is sufficient to determine the proportion of positive cells in the entire cancer area.     

乳腺癌耐药相关蛋白在乳腺癌的表达及与临床病理参数相关性

目的探讨原发性乳腺癌中乳腺癌耐药相关蛋白(BCRP)表达与临床指标及病理参数的相关性。方法采用免疫组织化学方法检测BCRP及雌激素受体α(ERα)、孕激素受体(PR)、HER-2、P53等病理参数的表达,应用Kruskal-Wallis秩和检验和Spearman相关性检验分析BCRP与临床指标及病理参数的相关性。结果原发性乳腺癌中BCRP表达阳性率64.39%,癌旁组织中BCRP表达阳性率33.33%,两者相比有显著性差异(X~2=9.323,P=0.002);BCRP表达水平与患者年龄、病理类型、临床分级及淋巴结转移无关,而与患者是否绝经有关,未绝经患者乳腺癌组织中BCRP表达水平显著高于已绝经患者(X~2=6.928,P=0.008);BCRP表达水平与ERα(r=0.204,P=0.019)和HER-2表达水平呈正相关(r=0.246,P=0.004),与PR、P53表达水平不具有相关性。结论乳腺癌中BCRP蛋白表达水平明显高于癌旁正常组织,其表达强度与与患者体内雌激素水平及ERα及HER-2强度正相关。     

Rationale for using raloxifene to prevent both osteoporosis and breast cancer in postmenopausal women

Both osteoporosis with fracture and breast cancer are important health issues for postmenopausal women. It is well known that estrogen and estrogen receptors (ERs) play an important role in the pathogenesis of both diseases. In past decades, hormone therapy (HT), mainly estrogen plus progestin (EPT), has been frequently used for the purpose of preventing and treating postmenopausal osteoporosis because of its efficacy, but it also contributes to a significant increase in breast cancer. Currently, there is a dilemma regarding the use of estrogen for postmenopausal women. Fortunately, an increasing understanding of the action of estrogen has led ultimately to the design of new drugs that work by virtue of their interaction with the ER; these drugs have come to be known as selective estrogen receptor modulators (SERMs), and are not only effective in preventing osteoporosis and managing those with osteoporosis, but also in decreasing the incidence of breast cancer. Among these SERMs, raloxifene may be the most attractive agent based on the evidence from five recent large trials (Multiple Outcomes of Raloxifene Evaluation [MORE], Continuing Outcomes Relevant to Evista [CORE], Raloxifene Use for the Heart [RUTH], Study of Tamoxifen and Raloxifene [STAR], and Evista Versus Alendronate [EVA]). The former three trials showed that raloxifene not only decreases the incidence of osteoporosis-associated fractures, but also has efficacy in breast cancer prevention. The head-to-head comparison with the anti-fracture agent alendronate (EVA trial) and the chemoprevention agent tamoxifen (STAR trial) further confirmed that raloxifene is a better choice. We concluded that since there is an absence of a therapeutic effect on relieving climacteric symptoms and there is the presence of a potential risk of thromboembolism in the use of raloxifene, this drug can be prescribed for clear indications, such as the management of osteoporosis, the prevention of fracture, and decreasing the incidence of invasive breast cancer, with careful monitoring for thromboembolism. It is reasonable to use raloxifene as an appropriate medicine that targets climacteric symptom-free postmenopausal women because of its overall favorable risk-benefit safety profile using the global index proposed by the Women's Health Initiation (WHI).     

Progress in endocrine approaches to the treatment and prevention of breast cancer

Tamoxifen had been the only available hormonal option for the systemic treatment for breast cancer from 1973 to 2000. Enormous efforts have led to the development of potent and selective third generation aromatase inhibitors including anastrozole, letrozole and exemestane. Due to their superior efficacy to tamoxifen, aromatase inhibitors are presently approved as first line agents for the treatment of advanced estrogen receptor (ER) positive breast cancer and adjuvant therapy in early ER positive early breast cancer in postmenopausal women. Selective ER Modulators (SERMS), tamoxifen and raloxifene are the only agents presently used in breast cancer prevention in high risk women and their use has increased substantially over the last decade. Third generations SERMS, lasofoxifene and bazedoxifene have shown significant reduction in bone loss compared to placebo in postmenopausal women and are currently approved in the European Union for the treatment of postmenopausal osteoporosis. This review outlines the current strategies employed in the use of endocrine therapy in the management and prevention of breast cancer.     

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in invasive breast cancer in women

Introduction

Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression are crucial in the biology of breast carcinoma. HER-2/neu gene is amplified and overexpressed in 15-30% of invasive breast cancers. HER-2-positive breast cancers have worse prognosis than HER-2 negative tumors and possess distinctive clinical features. The aim of this study was to assess the expression of HER2 in cancer tissue of patients with invasive breast cancer in correlation with tumor type, histological grade, tumor size, lymph node status, and expression of estrogen receptor and progesterone receptor.

Material and methods

Formalin-fixed, paraffin-embedded tissues from 40 patients with invasive HER-2-positive breast cancer and from 191 patients with HER-2-negative breast cancer were used in this study. HER2 expression was determined using the test HerceptTest™ DAKO.

Results

Among 231 cases of breast cancer, 18 invasive lobular carcinomas and 213 invasive ductal carcinomas were diagnosed. Sixty percent of HER-2-positive breast cancers were ER-positive compared with 77% in the HER-2-negative group (p = 0.002). The expression of PR was observed in 43% of HER-2-positive breast cancers and in 72% of HER2-negative tumors (p = 0.003). Excessive expression of HER2 protein was detected in 60% of patients positive for estrogen receptors, which may worsen prognosis in these patients.

Conclusions

Determination of HER2 overexpression in breast cancer patients, allows for a determination of a group of patients with a worse prognosis.