{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:00:41Z","timestamp":1783116041105,"version":"3.54.6"},"reference-count":20,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Uterine leiomyomas are the most common type of gynecologic tumor in women.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine the role of the cytokine receptor activator of nuclear factor \u03ba-\u0392 ligand (RANKL); its receptor, receptor activator of nuclear factor \u03ba-\u0392 (RANK); and the RANKL\/RANK pathway inhibitor RANK-Fc in leiomyoma growth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Messenger RNA (mRNA) or protein levels of RANKL, RANK, and proliferation markers cyclin D1 and Ki67 were assessed in various leiomyoma tissues and cell populations. Human xenograft experiments were performed to determine the effects of RANK-Fc on leiomyoma growth in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Research laboratory.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Twenty-four regularly cycling premenopausal women (age 28 to 49 years) who were not receiving hormone therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>None.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measure<\/jats:title>\n                  <jats:p>Tumor growth in a murine xenograft model following targeting of the RANKL\/RANK pathway with RANK-Fc.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>RANKL mRNA levels in leiomyoma were significantly higher than those in myometrial tissues. The highest RANK levels were found in the leiomyoma stem cell population, which is deficient in progesterone receptor (PR). Conversely, the highest RANKL levels were found in the PR-rich leiomyoma intermediate cell (LIC) population. R5020, a PR agonist, specifically increased RANKL expression in LICs. RANK-Fc blocked RANKL-induced expression of the proliferative gene cyclin D1. Treatment with RANK-Fc also significantly decreased tumor growth in vivo and diminished the expression of proliferation marker Ki67 in tumors (P &amp;lt; 0.01; n = 4).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Treatment with the RANKL\/RANK pathway inhibitor RANK-Fc significantly decreased human leiomyoma cell proliferation and tumor growth. This suggests that the RANKL\/RANK pathway could serve as a potential target for the prevention and treatment of uterine leiomyoma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2017-01585","type":"journal-article","created":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T18:02:43Z","timestamp":1521050563000},"page":"1842-1849","source":"Crossref","is-referenced-by-count":24,"title":["RANKL\/RANK Pathway and Its Inhibitor RANK-Fc in Uterine Leiomyoma Growth"],"prefix":"10.1210","volume":"103","author":[{"given":"Deborah E","family":"Ikhena","sequence":"first","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Kujawa","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ecem","family":"Esencan","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"V","given":"John S","family":"Coon","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Robins","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar E","family":"Bulun","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2018,3,14]]},"reference":[{"issue":"1","key":"2020071622281173700_B1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1067\/mob.2003.99","article-title":"High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence","volume":"188","author":"Baird","year":"2003","journal-title":"Am J Obstet Gynecol"},{"issue":"7","key":"2020071622281173700_B2","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1016\/j.fertnstert.2013.02.017","article-title":"Racial differences in fibroid prevalence and ultrasound findings in asymptomatic young women (18-30\u00a0years old): a pilot study","volume":"99","author":"Marsh","year":"2013","journal-title":"Fertil Steril"},{"issue":"2 Pt 1","key":"2020071622281173700_B3","first-page":"387","article-title":"ACOG practice bulletin. 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