Non-hormonal mediators of uterine fibroid growth

被引:18
作者
Cetin, Esra [1 ]
Al-Hendy, Ayman [1 ,2 ]
Ciebiera, Michal [1 ,3 ]
机构
[1] Univ Illinois, Dept Surg, 909 S Wolcott Ave, Chicago, IL 60612 USA
[2] Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA
[3] Ctr Postgrad Med Educ, Dept Obstet & Gynecol 2, Warsaw, Poland
基金
美国国家卫生研究院;
关键词
biology; leiomyoma; mediator; non-hormonal; pathophysiology; pharmacology; therapy; uterine fibroid; PROLIFERATOR-ACTIVATED RECEPTOR; LEIOMYOMA CELL-PROLIFERATION; NECROSIS-FACTOR-ALPHA; KAPPA-B ACTIVATION; RETINOIC ACID; WNT/BETA-CATENIN; SIGNALING PATHWAYS; HUMAN MYOMETRIAL; VITAMIN-D; EXTRACELLULAR-MATRIX;
D O I
10.1097/GCO.0000000000000650
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Purpose of review Uterine fibroids are the most common benign neoplasms of the female reproductive tract and one of the major public health concerns. Although most women with uterine fibroids are asymptomatic, over 30% of them will present with varying symptoms. This review focuses on the role of non-hormonal mediators and pathways in uterine fibroid biology. Furthermore, it provides data regarding the most recent findings in the field of compounds, which use those non-hormonal pathways in the medical therapy of uterine fibroids. Recent findings Complex signaling pathway alterations are crucial for uterine fibroid development. The topic of the pathophysiology of uterine fibroids focuses mostly on steroids and other hormones. However, other very important pathways exist, and some of them are independent of hormones. Some of the most important pathways, which are non-hormonal, but in some cases still hormone-depended, include growth factors, cytokines and inflammation, Smad proteins, wingless type/beta-catenin and others. Much more is known about hormonal than about non-hormonal signaling in uterine fibroids. Growth factors, early life exposure and inflammation are key factors in uterine fibroid biology. Numerous agents depend on those pathways and may find their place in the current and future therapy of uterine fibroids.
引用
收藏
页码:361 / 370
页数:10
相关论文
共 126 条
[1]   Uterine Fibroids: Burden and Unmet Medical Need [J].
Al-Hendy, Ayman ;
Myers, Evan Robert ;
Stewart, Elizabeth .
SEMINARS IN REPRODUCTIVE MEDICINE, 2017, 35 (06) :473-480
[2]   Silencing Med12 Gene Reduces Proliferation of Human Leiomyoma Cells Mediated via Wnt/β-Catenin Signaling Pathway [J].
Al-Hendy, Ayman ;
Laknaur, Archana ;
Diamond, Michael P. ;
Ismail, Nahed ;
Boyer, Thomas G. ;
Halder, Sunil K. .
ENDOCRINOLOGY, 2017, 158 (03) :592-603
[3]   Vitamin D3 Inhibits Wnt/β-Catenin and mTOR Signaling Pathways in Human Uterine Fibroid Cells [J].
Al-Hendy, Ayman ;
Diamond, Michael P. ;
Boyer, Thomas G. ;
Halder, Sunil K. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2016, 101 (04) :1542-1551
[4]   Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways [J].
Alarcon, Claudio ;
Zaromytidou, Alexia-Ileana ;
Xi, Qiaoran ;
Gao, Sheng ;
Yu, Jianzhong ;
Fujisawa, Sho ;
Barlas, Afsar ;
Miller, Alexandria N. ;
Manova-Todorova, Katia ;
Macias, Maria J. ;
Sapkota, Gopal ;
Pan, Duojia ;
Massague, Joan .
CELL, 2009, 139 (04) :757-769
[5]   Vitamin D and uterine fibroids: preclinical evidence is in; time for an overdue clinical study! [J].
Ali, Mohamed ;
Prince, Lillian ;
Al-Hendy, Ayman .
FERTILITY AND STERILITY, 2020, 113 (01) :89-90
[6]   Activation of β-Catenin Signaling and its Crosstalk With Estrogen and Histone Deacetylases in Human Uterine Fibroids [J].
Ali, Mohamed ;
Shahin, Sara Mahmoud ;
Sabri, Nagwa Ali ;
Al-Hendy, Ayman ;
Yang, Qiwei .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2020, 105 (04) :E1517-E1535
[7]   1,25 Dihydroxyvitamin D3 Enhances the Antifibroid Effects of Ulipristal Acetate in Human Uterine Fibroids [J].
Ali, Mohamed ;
Shahin, Sara Mahmoud ;
Sabri, Nagwa Ali ;
Al-Hendy, Ayman ;
Yang, Qiwei .
REPRODUCTIVE SCIENCES, 2019, 26 (06) :812-828
[8]   Successes and failures of uterine leiomyoma drug discovery [J].
Ali, Mohamed ;
Chaudhry, Zunir Tayyeb ;
Al-Hendy, Ayman .
EXPERT OPINION ON DRUG DISCOVERY, 2018, 13 (02) :169-177
[9]   RETINOIC ACID RECEPTORS AND RETINOID X-RECEPTORS - INTERACTIONS WITH ENDOGENOUS RETINOIC ACIDS [J].
ALLENBY, G ;
BOCQUEL, MT ;
SAUNDERS, M ;
KAZMER, S ;
SPECK, J ;
ROSENBERGER, M ;
LOVEY, A ;
KASTNER, P ;
GRIPPO, JF ;
CHAMBON, P ;
LEVIN, AA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (01) :30-34
[10]  
[Anonymous], 2020, BMJ BRIT MED J, DOI DOI 10.1136/BMJ.M1112