estrogen receptor

雌激素受体
  • 文章类型: Journal Article
    在这篇叙述性评论中,我们试图提供有关雌激素(受体)在皮肤黑色素瘤(CM)中的作用的证据的概述。我们回顾了从2002年到2022年的68项研究和4项系统评价和荟萃分析。雌激素受体β(ERβ)代替雌激素受体α(ERα)在CM中普遍存在,ERβ可能发挥保护作用,并且在进行性病例中检测到的频率较低。虽然患有CM的男性通常预后较差,随着年龄的增长,这种区别可能变得微不足道。口服避孕药(OC)和激素替代疗法(HRT)在CM中的作用仍存在争议。然而,最近的研究倾向于将使用这些外源激素与CM的风险增加联系起来,大多仅在使用雌激素治疗时,不与孕激素联合使用。相反,大多数研究发现体外受精(IVF)治疗对CM风险没有实质性影响.生殖因素,包括第一次分娩时年龄较小,更高的奇偶校验,缩短生殖寿命,显示相互矛盾的证据,一些研究表明CM风险较低。我们建议雌激素在CM中的重要作用。需要更多的研究,但是在黑色素瘤治疗中整合雌激素和靶向雌激素受体有望在该领域的未来发展。
    In this narrative review, we attempt to provide an overview of the evidence regarding the role of estrogen (receptors) in cutaneous melanoma (CM). We reviewed 68 studies and 4 systematic reviews and meta-analyses published from 2002 up to and including 2022. The prevailing presence of estrogen receptor β (ERβ) instead of estrogen receptor α (ERα) in CM is notable, with ERβ potentially playing a protective role and being less frequently detected in progressive cases. While men with CM generally experience a less favorable prognosis, this distinction may become negligible with advancing age. The role of oral contraceptives (OC) and hormone replacement therapy (HRT) in CM remains controversial. However, recent studies tend to associate the use of these exogenous hormones with a heightened risk of CM, mostly only when using estrogen therapy and not in combination with progesterone. On the contrary, the majority of studies find no substantial influence of in vitro fertilization (IVF) treatment on CM risk. Reproductive factors, including younger age at first childbirth, higher parity, and shorter reproductive life, show conflicting evidence, with some studies suggesting a lower CM risk. We suggest an important role for estrogens in CM. More research is needed, but the integration of estrogens and targeting the estrogen receptors in melanoma therapy holds promise for future developments in the field.
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  • 文章类型: Journal Article
    乳腺癌是全球最常见的癌症。大约70%的乳腺癌表达雌激素受体(ER),能够拮抗和降解ER(SERD)或共价结合并拮抗ER(SERCAs)的分子处于努力为患者带来更好治疗的最前沿。
    这篇综述总结了在2021年7月至2023年12月期间使用SciFinder鉴定的声称雌激素受体降解物(SERD)和共价拮抗剂(SERCA)的专利申请。对来自32个不同申请人的91项新专利申请进行了分层评估,分为酸性SERD,基本的SERD,SERCA和其他降解器。
    氟维司群在ER+乳腺癌治疗中的广泛采用继续刺激对口服生物可利用的SERD和SERCA的研究。许多分子已经进入临床开发,虽然有些已经停产,一组潜在的新疗法产生了令人鼓舞的疗效和安全性数据.值得注意的是,口头SERD的第一个例子,eelacstrant,现在已经被FDA和EMA批准了,进一步鼓励这类靶向治疗。
    UNASSIGNED: Breast cancer is the most frequently diagnosed cancer worldwide. With around 70% of breast cancers expressing the estrogen receptor (ER), molecules capable of antagonizing and degrading ER (SERDs) or covalently binding to and antagonizing ER (SERCAs) are at the forefront of efforts to bring better treatments to patients.
    UNASSIGNED: This review summarizes patent applications that claim estrogen receptor degraders (SERDs) and covalent antagonists (SERCAs) identified using SciFinder between the period July 2021 to December 2023. A total of 91 new patent applications from 32 different applicants are evaluated with stratification into acidic SERDs, basic SERDs, SERCAs and miscellaneous degraders.
    UNASSIGNED: The widespread adoption of fulvestrant in the treatment of ER+ breast cancer continues to stimulate research into orally bioavailable SERDs and SERCAs. A number of molecules have entered clinical development and, although some have been discontinued, a cohort of potential new treatments have generated encouraging efficacy and safety data. Notably, the first example of an oral SERD, elacestrant, has now been approved by the FDA and EMA, providing further encouragement for this class of targeted therapies.
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  • 文章类型: Journal Article
    目的:尚不清楚HER2阴性患者低雌激素受体(ER低)阳性早期乳腺癌(BC)受益于OncotypeDX®(ODX)测试。
    方法:我们对从乳腺生物标志物检测转诊中心转诊7年的ODX检测病例进行了回顾性回顾(n=854)。对于每种情况,我们记录了ODX复发评分(RS)以及ER核阳性百分比和免疫组化染色强度.我们的ER低标准定义为≤10%的细胞具有核阳性和/或弱染色强度。回顾了所有ER低病例的切片,并记录了报告的ODXER基因评分。我们随机选择了一个比较组的56名ER>10%阳性且染色强度非弱(ER高)的患者。
    结果:我们确定了27例(3.2%)符合我们的低ER标准。其中,92.6%的RS较高(>25),7.4%的RS为25。所有ER核阳性≤10%的病例均有较高的RS。大多数低ER病例(85.2%)的ODX定量ER基因评分在阴性范围,而所有(100%)ER高病例的ER基因评分均为阳性。
    结论:ODX似乎没有增加显著的额外信息来告知大多数ER低BC患者的治疗决策。除了低百分比的核阳性外,结合弱ER染色强度可识别约两倍的ER低患者,尽管对高RS的特异性降低。我们的研究支持以下论点:大多数ER低的早期BC应与ER阴性BC相似。
    OBJECTIVE: It remains unclear whether patients with HER2-negative, low-estrogen receptor (ER-low)-positive early breast cancer (BC) benefit from Oncotype DX® (ODX) testing.
    METHODS: We conducted a retrospective review of cases referred for ODX testing over a seven-year period from a breast biomarker testing referral center (n = 854). For each case, we recorded the ODX Recurrence Score (RS) along with percentage of ER nuclear positivity and staining intensity on immunohistochemistry. Our criteria for ER-low was defined as ≤10% cells with nuclear positivity and/or weak intensity of staining. Slides from all ER-low cases were reviewed and the reported ODX ER gene scores were recorded. We randomly selected a comparator group of 56 patients with ER > 10% positivity and non-weak staining intensity (ER-high).
    RESULTS: We identified 27 cases (3.2%) that met our criteria for ER-low. Of these, 92.6% had a high RS (>25), and 7.4% had a RS of 25. All cases with ≤10% ER nuclear positivity had a high RS. Most ER-low cases (85.2%) had ODX quantitative ER gene scores in the negative range, whereas all (100%) ER-high cases had positive ER gene scores.
    CONCLUSIONS: ODX does not appear to add significant additional information to inform treatment decisions for most patients with ER-low BC. Incorporating weak ER staining intensity in addition to low percentage of nuclear positivity identifies about twice as many ER-low patients, although with reduced specificity for high RS. Our study supports the contention that most ER-low early BC should be regarded similarly to ER-negative BC.
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  • 文章类型: Journal Article
    70%的乳腺癌患者有一个活跃的雌激素受体。他莫昔芬干扰雌激素与癌细胞结合的能力。他莫昔芬最具挑战性的方面,然而,乳腺癌细胞对其作用产生了抗性。一些研究表明,miRNA表达的改变对乳腺癌的耐药性有重要贡献。因此,本系统综述旨在研究显著影响他莫昔芬治疗反应的miRNAs.本研究遵循PRISMA说明。WebofScience,PubMed,搜索Scopus数据库以检索英语文章。搜索一直进行到2022年9月11日。搜索策略包括术语“他莫昔芬”,“乳腺肿瘤”,和“MicroRNA”。这项研究的纳入标准是英语,原创,以及研究对他莫昔芬治疗效果有效的miRNA的实验研究。共检索到565篇文献。筛选后,75项研究符合我们的纳入标准。这项系统综述研究检测了105个miRNAs,其中44项有积极作用,和47种miRNA抑制他莫昔芬功能。14个miRNAs有争议的作用,ie,一些研究显示了积极和消极的影响。对影响乳腺癌患者他莫昔芬功能的miRNA的研究可能有助于鉴定疾病复发风险较高的个体。相反,它可以潜在地利用适当的干预措施来有效地战胜耐药性。
    Seventy percent of breast cancer patients have an active estrogen receptor. Tamoxifen interferes with estrogen\'s ability to bind to cancer cells. The most challenging aspect of tamoxifen, however, is that breast cancer cells become resistant to its effects. Some studies have shown that alterations in miRNA expression contribute significantly to drug resistance in breast cancer. Therefore, the present systematic review aims to investigate miRNAs that significantly influence the response to tamoxifen treatment. The present study follows the PRISMA instructions. The Web of Science, PubMed, and Scopus databases were searched to retrieve English articles. The searches were conducted up to September 11, 2022. The search strategy included the terms \"Tamoxifen\", \"Breast Neoplasm\", and \"MicroRNA\". The inclusion criteria of this study are English, original, and experimental studies investigating miRNAs that are effective in the treatment efficacy of tamoxifen. A total of 565 articles were retrieved. After screening, 75 studies met our inclusion criteria. This systematic review study examined 105 miRNAs, of which 44 have a positive effect, and 47 miRNAs inhibit tamoxifen function. Fourteen miRNAs have a controversial effect, ie, some studies show positive and negative effects. The study of miRNAs affecting tamoxifen function in breast cancer patients may facilitate the identification of individuals at higher risk of disease recurrence. Conversely, it can potentially utilize appropriate interventions to defeat drug resistance effectively.
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  • 文章类型: Journal Article
    目的:雌激素和孕激素在维持妊娠中起关键作用,它们的功能是通过雌激素受体1(ESR1)/雌激素受体2(ESR2)和孕激素受体(PGR)介导的,分别。有人认为,ESR1,ESR2和PGR的遗传变异可能导致复发性妊娠丢失(RPL);然而,现有的证据仍然存在争议。本荟萃分析旨在探讨ESR1,ESR2和PGR基因的各种多态性与RPL风险的关系。
    方法:使用PubMed和Scopus进行了系统的文献检索,直至2023年8月,以获得相关研究。计算具有95%置信区间(95%CIs)的比值比(OR),并使用随机效应模型进行汇总以测试相关性。
    结果:共有31项具有12种不同多态性的研究,包括ESR1的5个多态性,ESR2的3个多态性和PGR的4个多态性,在本次荟萃分析中进行了分析。总的来说,在任何遗传分析模型中,ESR1和ESR2的各种多态性与RPL之间均未发现显着关系。PGRrs590688(C>G)多态性与显性下RPL升高风险显著相关(OR=1.67;95CI:1.15-2.44),等位基因(OR=1.55;95CI:1.13-2.12),和GCvs.CC(OR=1.55;95CI:1.07-2.23)模型。对于PGR基因的其他变体没有发现显著的关联。
    结论:与雌激素受体不同,PGRrs590688(C>G)的变化可能与RPL的风险增加有关。需要更多的研究来证实这一发现。
    OBJECTIVE: Estrogen and progesterone play key roles in the maintenance of pregnancy, and their function is mediated via estrogen receptor 1 (ESR1)/estrogen receptor 2 (ESR2) and progesterone receptor (PGR), respectively. It has been suggested the genetic variations in ESR1, ESR2, and PGR may contribute to recurrent pregnancy loss (RPL); however, the available evidence remains controversial. This meta-analysis aimed to explore the relation of various polymorphisms in ESR1, ESR2, and PGR genes to the risk of RPL.
    METHODS: A systematic literature search was conducted using PubMed and Scopus up to August 2023 to obtain relevant studies. The odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed and pooled with the use of random-effects models to test the associations.
    RESULTS: A total of 31 studies with 12 different polymorphisms, including 5 polymorphisms for ESR1, 3 polymorphisms for ESR2, and 4 polymorphisms for PGR, were analyzed in this meta-analysis. Overall, no significant relationship was found between various polymorphisms of ESR1 and ESR2 with RPL in any of the genetic analysis models. PGR rs590688 (C > G) polymorphism was significantly related to the elevated risk of RPL under the dominant (OR = 1.67; 95 %CI: 1.15-2.44), allelic (OR = 1.55; 95 %CI: 1.13-2.12), and GC vs. CC (OR = 1.55; 95 %CI: 1.07-2.23) models. No significant association was identified for other variants of PGR gene.
    CONCLUSIONS: Unlike estrogen receptors, variations in PGR rs590688 (C > G) may be linked to the increased risk of RPL. More studies are required to confirm this finding.
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  • 文章类型: Journal Article
    乳腺癌是一种常见的致命疾病,因此,有一个不断的研究,以寻找有效的目标和治疗方法。乳腺癌可以根据分子和组织学进行分类。乳腺癌可分为ER(雌激素受体)阳性和ER阴性,HER2(人表皮生长因子受体2)阳性和HER2阴性亚型基于特定生物标志物的存在。靶向激素受体,如HER2,孕激素受体(PR),ER,在乳腺癌的发生和发展中起着至关重要的作用。内分泌治疗和HER2靶向药物是目前针对这些受体使用的靶向治疗的实例。新兴的基于免疫的药物在乳腺癌的治疗中有希望的结果包括免疫检查点抑制剂,癌症疫苗,和过继性T细胞疗法。还探讨了免疫细胞和肿瘤微环境如何影响乳腺癌的发展和治疗反应。主要的生化途径,信令级联,以及参与乳腺癌发展和进展的DNA修复机制,包括PI3K/AKT/mTOR系统,MAPK通路,和其他人。这些途径旨在被多种靶向药物抑制,然后以恢复正常细胞功能为目标进行递送。这篇综述旨在通过总结不同的治疗方法来阐明乳腺癌的类型,这些方法可以针对定制药物的不同途径和更好的患者预后。
    Breast cancer is a common and deadly disease, so there is a constant need for research to find efficient targets and therapeutic approaches. Breast cancer can be classified on a molecular and histological base. Breast cancer can be divided into ER (estrogen receptor)-positive and ER-negative, HER2 (human epidermal growth factor receptor2)-positive and HER2-negative subtypes based on the presence of specific biomarkers. Targeting hormone receptors, such as the HER2, progesterone receptor (PR), and ER, is very significant and plays a vital role in the onset and progression of breast cancer. Endocrine treatments and HER2-targeted drugs are examples of targeted therapies now being used against these receptors. Emerging immune-based medicines with promising outcomes in the treatment of breast cancer include immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapy. It is also explored how immune cells and the tumor microenvironment affect breast cancer development and treatment response. The major biochemical pathways, signaling cascades, and DNA repair mechanisms that are involved in the development and progression of breast cancer, include the PI3K/AKT/mTOR system, the MAPK pathway, and others. These pathways are intended to be inhibited by a variety of targeted drugs, which are then delivered with the goal of restoring normal cellular function. This review aims to shed light on types of breast cancer with the summarization of different therapeutic approaches which can target different pathways for tailored medicines and better patient outcomes.
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  • 文章类型: Journal Article
    作为女性中最常见和最脆弱的恶性肿瘤,乳腺癌普遍表现出巨大的医疗保健挑战。从生物学和分子的角度来看,它是一种异质性疾病,根据驱动乳腺癌发生的病因进行分层。值得注意的是,遗传易感性和表观遗传影响通常构成该疾病的异质性。通常,乳腺癌在临床上本质上分为组织学亚型。这些分层使医生能够在乳腺癌疗法的范围内定制精确的治疗方法。在这种追求中,许多预后算法被广泛地表征,彻底改变了乳腺癌的描述方式。因此,理解乳腺癌的多学科原理以帮助新的治疗策略的发展是一个基本的必要条件.这篇综述旨在强调癌症的分子和遗传基础以及治疗和植物治疗背景。实质上,它还使研究人员深入了解乳腺癌细胞系作为乳腺癌研究干预的模型范例。
    As the most frequent and vulnerable malignancy among women, breast cancer universally manifests a formidable healthcare challenge. From a biological and molecular perspective, it is a heterogenous disease and is stratified based on the etiological factors driving breast carcinogenesis. Notably, genetic predispositions and epigenetic impacts often constitute the heterogeneity of this disease. Typically, breast cancer is classified intrinsically into histological subtypes in clinical landscapes. These stratifications empower physicians to tailor precise treatments among the spectrum of breast cancer therapeutics. In this pursuit, numerous prognostic algorithms are extensively characterized, drastically changing how breast cancer is portrayed. Therefore, it is a basic requisite to comprehend the multidisciplinary rationales of breast cancer to assist the evolution of novel therapeutic strategies. This review aims at highlighting the molecular and genetic grounds of cancer additionally with therapeutic and phytotherapeutic context. Substantially, it also renders researchers with an insight into the breast cancer cell lines as a model paradigm for breast cancer research interventions.
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  • 文章类型: Journal Article
    乳腺癌是全球女性中最常见和最致命的癌症。雌激素信号与激素依赖性乳腺癌(雌激素和孕激素受体阳性)密切相关,占肿瘤的三分之二。使用抗雌激素的激素疗法是金标准,但是对这些治疗的抗性总是通过各种生物学机制发生的,例如雌激素受体活性的变化,ESR1基因突变,PI3K通路的异常激活或细胞周期失调。所有这些因素导致了新疗法的发展,如选择性雌激素受体降解剂(SERD),或与细胞周期蛋白依赖性激酶(CDK)4/6或PI3K抑制剂的组合疗法。因此,了解雌激素途径对于激素依赖性癌症的治疗和新药开发至关重要。这篇小型综述总结了目前关于信号化的文献,雌激素受体在乳腺癌中的作用机制和临床意义。
    Breast cancer is the most common cancer and the deadliest among women worldwide. Estrogen signaling is closely associated with hormone-dependent breast cancer (estrogen and progesterone receptor positive), which accounts for two-thirds of tumors. Hormone therapy using antiestrogens is the gold standard, but resistance to these treatments invariably occurs through various biological mechanisms, such as changes in estrogen receptor activity, mutations in the ESR1 gene, aberrant activation of the PI3K pathway or cell cycle dysregulations. All these factors have led to the development of new therapies, such as selective estrogen receptor degraders (SERDs), or combination therapies with cyclin-dependent kinases (CDK) 4/6 or PI3K inhibitors. Therefore, understanding the estrogen pathway is essential for the treatment and new drug development of hormone-dependent cancers. This mini-review summarizes current literature on the signalization, mechanisms of action and clinical implications of estrogen receptors in breast cancer.
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  • 文章类型: Case Reports
    囊肿可以根据其胚胎背景进行隔离。在纵隔中发现的囊肿通常分为支气管囊肿,肠囊肿,食管囊肿,和非特异性囊肿。我们通过报道一例发生在60岁女性后纵隔的苗勒管囊肿,增加了关于这一主题的相对较小的文献,显示雌激素受体(ER)和PAX-8的弥漫性核阳性。我们检查并总结了文献中独特报道病例的发现。最后,我们对过去38.5年的所有后纵隔病变进行了机构回顾性审查.这表明,在我们自己的医疗保健系统内的135名候选人中,与纵隔苗勒管囊肿诊断一致的唯一病例是本文的报告.
    Cysts can be segregated according to their embryonic backgrounds. The cysts that were found in the mediastinum are usually divided into bronchogenic cysts, enteric cysts, esophageal cysts, and nonspecific cysts. We add to the relatively small body of literature that exists on this topic by reporting a case of a Müllerian cyst occurring in the posterior mediastinum of a 60-year-old female, showing diffuse nuclear positivity for estrogen receptor (ER) and PAX-8. We examined and summarized the findings of the unique reported cases in the literature. Lastly, an institutional retrospective review of all posterior mediastinal lesions in the last 38.5 years was performed. This revealed that out of 135 candidates within our own healthcare system, the only case consistent with the diagnosis of a mediastinal Müllerian cyst is the report included herein.
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  • 文章类型: Journal Article
    乳腺癌最近被认为是世界上女性的第一个致命恶性肿瘤。尽管现有的治疗方法改善了患者的预后,某些类型的乳腺癌是严重的治疗挑战。因此,正在努力提供更有效的治疗。隐丹参酮(CPT)是一种称为丹参的传统中草药的脂溶性二萜衍生物。在过去的几十年中,由于其巨大的治疗特性,包括抗肿瘤,抗炎,和抗纤维化。最近,研究发现,CPT通过不同的生理和免疫机制,在体内和体外表现出显著的抗乳腺癌作用。本研究总结了CPT对乳腺癌抗肿瘤作用的最新研究成果。Further,综述了基于乳腺癌类型和与其他药物联合应用的主要分子机制,为今后的纵向研究及其在乳腺癌治疗中的临床应用提供必要的证据。
    Breast cancer has recently been known as the first lethal malignancy in women worldwide. Despite the existing treatments that have improved the patients\' prognosis, some types of breast cancer are serious challenges to treat. Therefore, efforts are underway to provide more efficient therapy. Cryptotanshinone (CPT) is a liposoluble diterpenoid derivation of a traditional Chinese herbal medicine called Salvia miltiorrhiza Bunge. It has been considered in the past decades due to its vast therapeutic properties, including anti-tumor, anti-inflammatory, and anti-fibrosis. Recently, studies have found that CPT showed a significant anti-breast cancer effect in vivo and in vitro through different physiological and immunological mechanisms. This study summarized the latest research findings on the antitumor effect of CPT in breast cancer. Further, the main molecular mechanisms based on breast cancer types and combination with other drugs were reviewed to provide essential evidence for future longitudinal research and its clinical application in breast cancer treatment.
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