黑色素瘤的内分泌途径:雌激素受体表达之谜

IF 0.1 Q4 MEDICINE, GENERAL & INTERNAL
F. Șandru, A. Popa, M. Dumitrașcu, Ruxandra D. Sinescu-Bălțăteanu, Ș. Bucur, M. Carsote
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引用次数: 0

摘要

“黑色素瘤的结局在女性和男性之间似乎不同,雌激素(E)通过雌激素受体(ER)在肿瘤中的表达发挥潜在的保护作用。在ER的研究中,αα和β(ERβ)都是非黑色素瘤肿瘤(如乳腺癌和癌症)中众所周知的内分泌成分。免疫组织化学(IHC)关于ER的黑色素瘤评估代表了一条探索肿瘤特征的途径,以提供有关预后和潜在辅助治疗的有用信息。目前,这不是一种常规做法,也不是决定药物治疗的强制性步骤。通常,IHC是基于关于ER配置的乳腺肿瘤常用试剂盒。先前/同时使用口服避孕药和激素替代疗法与黑色素瘤的更好预后无关;它们都不是黑色素瘤幸存者的禁忌症;肿瘤的一个子集可能表现出更高的ER表达,其可能被基于激素的治疗作为SERM(选择性雌激素受体调节剂)(例如他莫昔芬)靶向。对黑色素瘤细胞系的实验研究证实了ERβ的抗肿瘤活性,这可能是一种预后标志物。黑色素细胞和角质形成细胞中的G蛋白偶联雌激素受体也可能参与其中。TGF-β(转化生长因子β)、IGF1(胰岛素样生长因子)和ERα表达的额外串扰参与肿瘤发生途径。最近的临床前研究表明,ERβ的选择性激动剂二芳基丙腈具有潜在的益处;吡唑衍生物21-23可以阻断ER。小鼠黑色素瘤模型显示了抗雌激素药物(如分子富维司琼)的干扰,以增强免疫检查点阻断,这是一种治疗实体癌的现代方法。黑色素瘤的增殖可能部分由ER解释;这是否普遍适用,或者是否存在与E状态特别相关的肿瘤亚群,仍有争议。黑色素瘤中E状态的主题目前还远不清楚,有必要对这一特定问题进行进一步的研究,以将其作为一种实用的方法来实施,这种疾病目前仍有非常严重的预后。”
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Endocrine Approach of Melanoma: The Puzzle of Estrogen Receptors Expression
"Melanoma outcome seems different between females and males, with a potential protective role of estrogen (E) through estrogen receptors (ER) expression into the tumor. In the study of ERs, both alfa (ERα) and beta (ERβ) is a well-known endocrine elements in non-melanoma tumors, like mammary and endometrial cancer. Immunohistochemistry (IHC) assessment of melanoma concerning ERs represents a path to explore the tumor profile to provide useful information concerning the prognostic and potential adjuvant treatment. Currently, this is not a routine practice, nor a mandatory step for deciding the medical therapy. Typically, IHCs are based on usual kits for mammary tumors regarding ERs configuration. Prior/concomitant use of oral contraceptives and hormonal replacement therapy is not correlated with a better prognostic in melanoma; neither have they represented a contraindication for survivors of melanoma; a subset of tumors might present a higher ER expression which is potentially targeted by the hormone-based treatment as SERMs (Selective Estrogen Receptors Modulator), for instance, tamoxifen. Experimental studies on melanoma cell lines confirmed the anti-tumor activity of ERβ which might function as a prognostic marker. G-protein-coupled estrogen receptors in melanocytes and keratinocytes might be involved, too. Additional crosstalk of TGF-β (Transforming Growth Factor β), respective IGF1 (Insulin-like Growth Factor), and ERα expression are involved in tumorigenic pathways. Recent preclinical studies showed the potential benefits of diarylpropionitrile, a selective agonist of ERβ; pyrazole derivates 21-23 can block ERs. Murine melanoma models showed the interference of anti-estrogenic medication (like molecule fulvestrant) to enhance immune checkpoint blockade, a modern approach to solid cancers. The proliferation of melanoma might be partially explained by ERs; whether this is generally applicable or there is a subgroup of tumors particularly related to E status is still debatable. The subject of E status in melanoma is far from clear at this point and further studies are necessary concerning this particular issue to implement it as a practical approach in the daily management of a disease that still has a very severe prognostic nowadays "
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来源期刊
Romanian Journal of Military Medicine
Romanian Journal of Military Medicine MEDICINE, GENERAL & INTERNAL-
自引率
33.30%
发文量
2
审稿时长
12 weeks
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