共查询到18条相似文献,搜索用时 296 毫秒
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目前第三代芳香化酶抑制剂(Aromatase Inhibitors,AIs)已广泛应用于早期及转移性乳腺癌的辅助治疗。为绝经后激素受体阳性乳腺癌患者的治疗提供了新的一条途径。然而,由于AIs抑制绝经后乳腺癌患者体内雄激素转变为雌激素过程中芳香化酶的活性导致体内雌激素水平降低,而雌激素对骨组织具有保护作用,因此服用芳香化酶抑制剂的患者将会出现骨丢失。 相似文献
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芳香化酶基因(CYP19)编码的芳香化酶是催化雄激素向雌激素转化的关键酶,CYP19的变异可使芳香化酶活性改变,导致雌激素水平的改变,从而使乳腺癌易感性发生改变,也可能影响到乳腺癌内分泌治疗的敏感性。现综述CYP19多态性与乳腺癌易感性及其治疗相关性。 相似文献
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人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)过表达型乳腺癌是乳腺癌中具有侵袭性的亚型之一,与其他类型乳腺癌相比,此类型疾病进展迅速,易复发转移,且预后差。近年来,研究表明雄激素受体(androgen receptor,AR)在HER-2过表达型乳腺癌中高表达。因此,本文将对AR在HER-2过表达型乳腺癌中的作用机制,对预后的影响及最新研究进展进行综述,以期为未来研究提供新的思路。 相似文献
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他莫昔芬(tamoxifen,TAM)为人工合成的非甾体类抗雌激素药物,被普遍的应用于雌激素受体(estrogen receptor,ER)阳性的乳腺癌患者中。但大约一半的ER阳性的患者会出现耐药。可见内分泌耐药是当前临床迫切需要解决的问题。随着对耐药机制的深入研究:发现雄激素受体(androgen receptor,AR)在 72.9%的原发性乳腺癌病例中表达,并在约65%的乳腺癌中与ER同时表达。有研究显示:AR/ER越高预示着TAM治疗率越低;AR与人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)之间所形成的正反馈循环能够增加TAM耐药;AR、髓样细胞白血病-1蛋白(myeloid cell leukemia-1,Mcl-1)与TAM耐药有可能相关。所以探讨AR在TAM耐药中的作用和机制是非常有意义的。为乳腺癌的靶向治疗掀开了新的一页。 相似文献
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自1977年Kiang等在胃癌组织中首次发现雌激素受体(ER)后,人们开始逐渐发现性激素受体不仅在性激素依赖器官中存在,后来又发现胃癌组织中存在孕激素受体(PGR)以及雄激素受体(AR)。近年来有关非性激素靶器官肿瘤胃癌中ER、PGR和AR的研究较多。本文对胃癌中AR的表达作用机制、检测方法以及其与胃癌的临床生物学行为的相关性进行综述。 相似文献
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Damoun Safarpour Shabnam Pakneshan Fattaneh A Tavassoli 《American journal of cancer research》2014,4(4):353-368
Background: Triple negative breast carcinomas (TNBC) do not benefit from hormonal or Herceptin therapies. In search of novel therapeutic targets for TNBC, interest is escalating in a subset of these tumors that are androgen receptor (AR) positive with potential benefit from anti-androgen therapy. Against this background, the frequency of AR expression alone and in combination with other markers and morphologic features was assessed to identify TNBC subtypes for targeted therapy. Methods: 400 consecutive invasive mammary carcinomas with known estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and HER2 status were selected for study. The frequency of AR positivity alone or in combination with other markers was recorded with specific attention to the morphology of AR+ TNBCs. Ki67 was evaluated in selected group of cases. ASCO/CAP guidelines were used for interpretation of the various biomarkers. Results: Of the 400 tumors, 32 (8%) carcinomas were quadruple negative (ER-, PR-, AR-, Her2-), while 50 tumors (12.5%) were triple negative (ER-, PR-, Her2-); 18 (36%) of the triple negative tumors were AR positive and 10 (55%) of these were classic apocrine carcinomas. Fourteen cases, all apocrine carcinomas, were AR and Her2 positive. All 32 QN carcinomas were poorly differentiated and they had the highest Ki67 labeling index. Conclusion: The relatively high proportion of AR+ tumors (36%) among the 50 triple negative carcinomas is an important finding in support of routine assessment of AR in at least all TNBCs and apocrine carcinomas as a potential target for therapy. 相似文献
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Breast cancer occurs at a high frequency in women and, given this fact, a primary focus of breast cancer research has been the study of estrogen receptor α (ER) signaling. However, androgens are known to play a role in normal breast physiology and therefore androgen receptor (AR) signaling is becoming increasingly recognized as an important contributor towards breast carcinogenesis. Moreover, the high frequency of AR expression in breast cancer makes it an attractive therapeutic target, but the ability to exploit AR for therapy has been difficult. Here we review the historical use of androgen/anti-androgen therapies in breast cancer, the challenges of accurately modeling nuclear hormone receptor signaling in vitro, and the presence and prognostic significance of AR in breast cancer. 相似文献
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Androgens have a dual effect on mammary cells. Indeed, they have an influence on mammary cells proliferation thanks to several possible mechanisms, including their transformation into dihydrotestosterone (5alpha-reductase pathway) or into estradiol (aromatase pathway) or their binding to the androgen receptor (AR) and/or to the estrogen receptor (ER). Androgen signaling, using 5alpha-reductase pathway, enables the control of cell proliferation, mediated by AR. So androgen signaling plays a crucial role in breast homeostasis, negating the proliferative effects of estrogen signaling in the breast. When androgens transform into estrogens (aromatase pathway), they increase cell proliferation and mammary carcinogenesis risk. High levels of androgens and estrogens in the serum are associated with increased incidence of postmenopausal breast cancers. Genetic variations in metabolic genes (CYP11, CYP19) and in the AR gene are both involved in dual effects of androgens. Since mammary cells metabolic enzymes vary with time, aging increases the risk of breast cancer induced by estrogens and androgens. In addition, AR function can be perturbed by low doses of synthetic progestin, acting as endocrine disruptors to negate the protective effects of androgen signaling in the breast. In the future, the determination of AR expression in infiltrative breast cancer specimens and circulating androgens levels could provide additional information about hormonal dependency and prognosis of breast carcinomas. 相似文献
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Estrogen plays crucial roles in the progression of hormone-dependent breast cancers through activation of nuclear estrogen receptor α (ER). Estrogen is produced locally from circulating inactive steroids and adrenal androgens in postmenopausal women. However, conversion by aromatase is a rate-limiting step in intratumoral estrogen production in breast cancer. Aromatase inhibitors (AIs) inhibit the growth of hormone-dependent breast cancers by blocking the conversion of adrenal androgens to estrogen and by unmasking the inhibitory effect of androgens, acting via the androgen receptor (AR). AIs are thus a standard treatment option for postmenopausal hormone-dependent breast cancer. However, although initial use of AIs provides substantial clinical benefit, some breast cancer patients relapse because of the acquisition of AI resistance. A better understanding of the mechanisms of AI resistance may contribute to the development of new therapeutic strategies and aid in the search for new therapeutic targets and agents. We have investigated AI-resistance mechanisms and established six AI-resistant cell lines. Some of them exhibit estrogen depletion-resistance properties via constitutive ER-activation or ER-independent growth signaling. We examined how breast cancer cells can adapt to estrogen depletion and androgen superabundance. Estrogen and estrogenic androgen produced independently from aromatase contributed to cell proliferation in some of these cell lines, while another showed AR-dependent cell proliferation. Based on these findings, currently proposed AI-resistance mechanisms include an aromatase-independent estrogen-producing pathway, estrogen-independent ER function, and ER-independent growth signaling. This review summarizes several hypotheses of AI-resistance mechanisms and discusses how existing or novel therapeutic agents may be applied to treat AI-resistant breast cancers. 相似文献
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Suzuki T Miki Y Moriya T Akahira J Ishida T Hirakawa H Yamaguchi Y Hayashi S Sasano H 《International journal of cancer. Journal international du cancer》2007,120(2):285-291
Previous in vitro studies demonstrated that bioactive androgen 5alpha-dihydrotestosterone (DHT) exerted antiproliferative effects through an interaction with androgen receptor (AR) in breast carcinoma cells. However, AR status has not been examined in association with DHT concentration in breast carcinoma tissues, and significance of androgenic actions remains unclear in breast carcinomas. Therefore, in our study, we first examined intratumoral DHT concentrations in 38 breast carcinoma tissues using liquid chromatography/electrospray tandem mass spectrometry. Intratumoral DHT concentration was positively associated with 5alpha-reductase type 1 (5alphaRed1), and negatively correlated with aromatase. We then examined clinical significance of AR and 5alphaRed1 status in 115 breast carcinoma tissues by immunohistochemistry. Breast carcinomas positive for both AR and 5alphaRed1 were inversely associated with tumor size or Ki-67. These patients showed significant associations with a decreased risk of recurrence and improved prognosis for overall survival, and the AR / 5alphaRed1 status was demonstrated an independent prognostic factor. Moreover, we examined possible regulation of DHT production by aromatase in in vitro studies. DHT synthesis from androstenedione in MCF-7 cells was significantly inhibited by coculture with aromatase-positive stromal cells, which was significantly reversed by addition of aromatase inhibitor exemestane. These results suggest that intratumoral DHT concentration is mainly determined by 5alphaRed1 and aromatase in breast carcinoma tissues, and antiproliferative effect of DHT may primarily occur in the cases positive for both AR and 5alphaRed1. Aromatase inhibitors may be more effective in these patients, possibly due to increasing local DHT concentration with estrogen deprivation. 相似文献
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目的:探讨乳腺癌的钼靶x线表现与雌激素受体(ER)、孕激素受体(PR)以及人表皮生长因子受体-2(C—erbB-2)表达之间的关系。方法:将111例经手术病理证实的乳腺癌患者钼靶X线征象中的肿块、钙化、结构扭曲、毛刺与ER、PR、C—erbB-2表达情况进行比较。结果:111例中,有肿块67例(60.36%),有毛刺22例(19.82%),有钙化者41例(36.94%),有结构扭曲者21例(18.92%)。ER阳性59例(53.15%),PR阳性46例(41.44%),C—erbB-2阳性56例(50.45%)。肿块、钙化和结构扭曲与ER的表达无显著统计学意义;有毛刺组的ER阳性表达高于无毛刺组,有显著统计学意义。肿块、钙化、结构扭曲和毛刺均与PR的表达无显著统计学意义。有肿块组中C—erbB-2阳性表达低于无肿块组;有钙化组的C—erbB-2阳性表达高于无钙化组,都有显著统计学意义。结构扭曲和毛刺与C—erbB-2的表达没有显著统计学意义。结论:乳腺癌患者的钼靶X线表现可在某种程度上反映ER、PR、C—erbB-2的表达状况。 相似文献
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激素受体ER与PR及AR在男性乳腺癌与良性病变组织中的表达 总被引:5,自引:1,他引:4
目的:探讨激素受体(ER、PR和AR)在男性乳腺癌的表达及三种受体之间表达的相关关系。方法:采用免疫组化方法对ER、PR、AR三种受体进行检测,并用SPSS软件分析各组差异。结果:ER、PR在23例男性乳腺癌患者组织中表达阳性率较良性病变低,分别为82.6%、56.5%与良性疾病相比有明显的统计学差异(OR分别为:4.32和5.25,P<0.05),AR表达与ER、PR之间表达不相关。结论:男性乳腺癌患者中ER、PR表达阳性率较良性病变低,AR表达与ER、PR之间表达不相关。 相似文献