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芳香化酶抑制剂与骨骼

Aromatase inhibitor and bone.

作者信息

Miki Yasuhiro, Suzuki Takashi, Sasano Hironobu

机构信息

Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980 8575, Japan.

出版信息

Biomed Pharmacother. 2007 Oct;61(9):540-2. doi: 10.1016/j.biopha.2007.08.011. Epub 2007 Sep 14.

Abstract

Aromatase is a key enzyme of intratumoral production of estrogen in breast cancers. Aromatase inhibitors are commonly used as hormone therapy in postmenopausal estrogen sensitive breast cancer patients. Type I aromatase inhibitors such as exemestane are steroidal inhibitors, which have androstenedione like structure and bind to androgen receptor with low affinity. Type II aromatase inhibitors such as anastrozole and letrozole are known as non-steroidal inhibitors, which are non-competitive inhibitors of aromatase. Sex steroid hormones such as estrogen and androgen play important roles in the maintenances of female and male bone tissues. It is well known that adult women have less bone mass than men. Especially after menopause, adult women loss their bone mass more rapidly than men of comparable age do. Therefore, many clinical reports of breast cancer patients treated with aromatase inhibitors have emphasized potential bone loss caused by aromatase inhibition. Several basic researches using animal model or in vitro model demonstrated the different effects of steroid and non-steroid aromatase inhibitors on bone tissues and cells. In this review, we summarize the effects of AIs on bone tissues reported in clinical studies and animal/in vitro studies.

摘要

芳香化酶是乳腺癌肿瘤内雌激素生成的关键酶。芳香化酶抑制剂通常用作绝经后雌激素敏感性乳腺癌患者的激素疗法。依西美坦等I型芳香化酶抑制剂是甾体类抑制剂,具有类似雄烯二酮的结构,与雄激素受体的亲和力较低。阿那曲唑和来曲唑等II型芳香化酶抑制剂被称为非甾体类抑制剂,是芳香化酶的非竞争性抑制剂。雌激素和雄激素等性甾体激素在维持女性和男性骨组织方面发挥着重要作用。众所周知,成年女性的骨量比男性少。尤其是绝经后,成年女性骨量流失比同龄男性更快。因此,许多关于接受芳香化酶抑制剂治疗的乳腺癌患者的临床报告都强调了芳香化酶抑制导致的潜在骨量流失。几项使用动物模型或体外模型的基础研究证明了甾体和非甾体芳香化酶抑制剂对骨组织和细胞的不同影响。在本综述中,我们总结了临床研究以及动物/体外研究中报道的芳香化酶抑制剂对骨组织的影响。

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