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绝经后妇女雌激素受体(ER)基因XbaⅠ限制性片断长度多态性(RFLP)与骨密度的关系
目的研究绝经后妇女ER基因XbaⅠ限制性片断长度多态性(RFLP)与骨密度、骨生化指标和停经年限的关系.方法用PCR-RFLP方法检测绝经后妇女的ER基因型;DEXA检测腰椎和股骨各处骨密度,同时测定血骨钙素、尿吡啶并酚等骨转换指标.结果在205例绝经后妇女中发现XX、Xx和xx基因型频率分别为6.8%、25.9%和67.3%,XX基因型的妇女虽然停经时间更长,但腰椎骨密度仍高于Xx和xx型.结论 ER基因XX型可能对腰椎骨量的维持有一定作用.
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绝经期激素及其相关治疗与血栓栓塞性疾病
绝经期激素补充治疗(hormone replacement therapy, HRT)与发生血栓栓塞性疾病的关系,一直受到关注.1996年,美国预防服务工作组( U.S. Preventive Services Task Force, USPSTF)总结、分析有关文献后认为,应用HRT不增加发生静脉血栓的风险.之后,逐渐有大规模、随机、对照以及队列研究的文章发表.本文综合有关文献,对绝经期应用HRT、选择性雌激素受体调节剂(selective estrogen receptor modulators,SERMs),与绝经后妇女发生血栓栓塞性疾病的关系,综述如下.
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选择性雌激素受体调节剂雷洛昔芬的临床研究进展
激素补充治疗可改善妇女更年期症状,降低骨折率,但长期使用可增加乳腺癌的风险[1].雷洛昔芬(raloxifen)为一种选择性雌激素受体调节剂(selective estrogen receptor modulator,SERM),由于其对骨骼具有保护作用,可降低血脂,对乳腺和子宫内膜无刺激作用,已被美国食品卫生管理局批准用于绝经后妇女骨质疏松的预防和治疗.
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黄酮、异黄酮药物抑制肿瘤细胞增殖作用的新进展
目的黄酮和异黄酮是具有多种药理功能的药物,从抑制肿瘤细胞恶性增殖的角度阐明其药理作用.方法总结新文献,对黄酮和异黄酮的药物机制加以综述.结果黄酮和异黄酮具有抑制蛋白酪氨酸激酶、抑制拓扑异构酶、抑制CDK(cyclin depend kinase)、SERM(selective estrogen receptor mediator)等作用.结论黄酮和异黄酮可以作用于上述多个靶点抑制肿瘤细胞恶性增生.
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几度吹唤——喜睹内分泌治疗药研发新貌
1选择性雌激素受体调节剂用于防治骨质疏松选择性雌激素受体调节剂(Selective estrogen receptor modulator,SERM)是一类人工合成的非激素制剂,可与雌激素受体结合,选择性地作用于不同组织的雌激素受体,在不同的靶组织分别产生类雌激素或抗雌激素作用.由于不同结构的特点,对各种受体的亲和力可有所差异,从而在组织中发挥不同的生物效应.主要品种有他莫昔芬、雷洛昔芬、屈洛昔芬.与第1代他莫昔芬相比,雷洛昔芬抗雌激素作用更强,雌激素样作用更弱.当雌激素受体被配体如17-β雌二醇激活后,受体-配体复合物形成,并和热休克蛋白脱离后形成二聚体,二聚体和不同基因启动区的雌激素应答单位结合形成雌激素-受体-DNA复合物,刺激基因转录.雷洛昔芬与雌激素与雌激素受体结合的部位相同,但两者的结合力、结合机制、导致受体结合结构的变化的差异是不同基因转录的原因.雌激素和雷洛昔芬对靶器官作用不同的其他原因尚有受体多发亚型、不同受体亚型的激活和对抗作用及受体亚型选择性表达有关.
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选择性雌激素受体调节剂雷洛昔芬的临床研究进展
激素补充治疗可改善妇女更年期症状,降低骨折率,但长期使用可增加乳腺癌的风险.雷洛昔芬(raloxifen)为一种选择性雌激素受体调节剂(selective estrogen receptor modulator,SERM),由于其对骨骼具有保护作用,可降低血脂,对乳腺和子宫内膜无刺激作用,已被美国食品卫生管理局批准用于绝经后妇女骨质疏松的预防和治疗.
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选择性雌激素受体调节剂——雷洛昔芬的药理及临床应用
雷洛昔芬是继三苯氧胺之后的新一代选择性雌激素受体调节物(selective estrogen receptor modulator,SERM),它对乳腺组织及子宫内膜具有抗雌激素样的作用,而在骨组织中呈现雌激素样活性,同时具有改善血脂的作用.众所周知,激素补充治疗是更年期妇女保健中的重要措施,除可以缓解更年期综合征症状外,还具有抑制骨吸收、防止骨质疏松及改善血脂等作用.
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儿童鞘膜积液对其睾丸附件的影响
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抗雌激素药物的研究进展
三苯氧胺(tamoxifen,TAM)在乳腺癌治疗中有显著的作用,然而一些新兴的抗雌激素药物已经诞生.这些药物包括新的选择性雌激素受体调节剂(selective estrogen receptor modulators,SERMs)和选择性雌激素受体下调剂(selective estrogen receptor downregulators,SERDs).SERD也就是以前所说的纯抗雌激素物质,它的研究成为当今乳腺癌研究的一大热点.
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他莫昔芬致子宫内膜病变的宫腔镜诊治
他莫昔芬(Tamoxifen ,TAM)是第一代选择性雌激素受体调节剂(Selective estrogen receptor modulators,SERMs),对不同靶器官间有雌激素和(或)抗雌激素样的双重作用.70年代初TAM用于治疗晚期乳腺癌,70年代末用于乳腺癌的辅助治疗.1983年首次报道服用TAM两年可提高乳癌患者生存率.1985年一项随机、前瞻性科研证实TAM能抑制对侧乳腺癌发生,危险性减少35%~50%,同时明显提高生存率.以后一系列的临床研究证实术后化疗辅助TAM治疗是乳癌合理的治疗方案.但是,随着乳癌发生率的不断升高和TAM的广泛应用,TAM引起子宫内膜病变的现象越来越受到人们的重视.
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Quantitative detection of metastasis-associated1mRNA and protein expression in breast cancer
Objective Understanding the mechanism of breast cancer metastasis will benefit those patients in need of aggressive treatment and avoid side effects caused by chemotherapy over treatment.Recently,a potential metastasis-associated gene and its product,the metastasis-associated 1 (MTA1),were identified; this gene has been found to be overexpressed in a variety of cancers.Methods In the present study,therefore,the level of expression of MTA1 mRNA has been assessed by LightCycler quantitative real-time RT-PCR in 160 cases of invasive carcinoma of the breast.MTA1 protein expression level was also detected by immunohistochemistry from available paired tissues of 154 cases.Associations between MTA1 mRNA and protein expression and clinicopathological factors were analyzed.Results It was found that MTA1 mRNA was expressed at significantly higher levels in patients with negative lymph node status,with ER and PgR positive and HER2 negative tumor.No difference was found between patient age,tumor size and histological grade groups.Patients with high levels of expression of MTA1 mRNA had a better prognosis than those with low expression.However,no difference was found between the protein level and clinicopathological factors.Univariate and multivariate prognostic analysis did not demonstrate that MTA1 mRNA was an independent prognostic factor for breast cancer.Conclusion In breast cancer,inconsistent with other tumor types,MTA1 gene expression is correlated with non-invasive clinicopathological factors and longer survival,which might suggest MTA1 gene is a tumor type specific metastasis associated gene.
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Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast
Estrogen is well-established as a mitogenic factor implicated in the tumorigenesis and progression of breast cancer via its binding to the estrogen receptor a(ERα). Recent data indicate that chromatin inactivation mediated by histone deacetylation(HDAC) and DNA methylation is a critical component of ERα silencing in human breast cancer cells. The aim of this study was to determine the expression of the HDAC1 gene in malignant human breast tissue and to correlate our observations with available clinical information. In the present study, the level of expression of HDAC1 mRNA was assessed by LightCycler-based quantitative real-time reverse transcriptase (RT)-PCR analvsis in 162 cases of invasive carcinoma of the breast. Associations between HDAC1 mRNA expression and different clinicopathological factors were sought. It was found that HDAC1 mRNA was expressed at significantly higher levels in tumors from patients over 50 years of age and in those tumors without axillary lymph node involvement, that are less than 2 cm, that are of a non-high histological grade, that are HER2 negative and that are ERα/PgR positive. Patients with tumors displaying high levels of HDAC1 mRNA expression tended to have a better prognosis in terms of both disease-free and overall survival. However, univariate and multivariate analysis did not show HDAC1 mRNA expression level to be an independent prognostic factor for either disease-free or overall survival. These results imply that HDAC1 mRNA expression could have potential as an endocrine response marker and may have prognostic implications for breast cancer progression.
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Chemotherapy, endocrine therapy and molecular targeted therapy are vital means in the treatment of metastatic breast cancer (MBC), whose reasonable and standard applications are of great importance to prolong patients’ survival and improve the quality of life. The expressions of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) present signiifcant differences between primary and metastatic breast cancer. However, these differences may affect the selection of MBC patients for therapeutic strategies and judgment on the prognosis. Hence, the relevant researches on variations of hormone receptors and HER-2 in primary and metastatic breast cancer, discordant causes of ER, PR and HER-2 expression in primary and metastatic lesions and clinical value of biopsy to the metastases are reviewed in the study.
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Chemotherapy, endocrine therapy and molecular targeted therapy are vital means in the treatment of metastatic breast cancer (MBC), whose reasonable and standard applications are of great importance to prolong patients’ survival and improve the quality of life. The expressions of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) present signiifcant differences between primary and metastatic breast cancer. However, these differences may affect the selection of MBC patients for therapeutic strategies and judgment on the prognosis. Hence, the relevant researches on variations of hormone receptors and HER-2 in primary and metastatic breast cancer, discordant causes of ER, PR and HER-2 expression in primary and metastatic lesions and clinical value of biopsy to the metastases are reviewed in the study.