Linked Life Data

20414849

Source:http://linkedlifedata.com/resource/pubmed/id/20414849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-4-23
pubmed:abstractText
Although the traditional concept supports a crucial role of estrogen in promoting leiomyoma growth, unequivocal evidence has emerged indicating that progesterone also plays a vital role in the regulation of leiomyoma growth. Recent clinical trials have demonstrated the efficacy of asoprisnil, a selective progesterone receptor modulator, and CDB-2914, a novel progesterone receptor modulator, for the treatment of women with symptomatic leiomyomata. These compounds significantly reduced leiomyoma and uterine volume and improved leiomyoma-related symptoms without serious complications. However, the precise mechanism whereby these compounds cause leiomyoma regression remains poorly understood. Our extensive in vitro studies have provided novel evidence for the growth inhibitory effects of asoprisnil and CDB-2914 on cultured leiomyoma cells. Both compounds exhibited antiproliferative, proapoptotic, and antifibrotic actions on cultured leiomyoma cells in the absence of comparable effects on cultured normal myometrial cells. Asoprisnil and/or CDB-2914 modulated the ratio of progesterone receptor isoforms (PR-A and PR-B) in cultured leiomyoma cells; decreased the cell viability; suppressed the expression of growth factors, angiogenic factors, and their receptors in those cells; and induced apoptosis through activating the mitochondrial and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathways and eliciting endoplasmic reticulum stress. Furthermore, these compounds suppressed types I and III collagen synthesis by modulating extracellular matrix-remodeling enzymes in cultured leiomyoma cells without affecting those syntheses in cultured normal myometrial cells. These findings indicate that both compounds exert antiproliferative, proapoptotic, and antifibrotic actions on leiomyoma cells in a cell-type specific manner. This supports the notion that asoprisnil and CDB-2914 hold promise for the nonsurgical treatment of uterine leiomyomata.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1526-4564
pubmed:author
pubmed:copyrightInfo
Thieme Medical Publishers.
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
260-73
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Cell-type specific actions of progesterone receptor modulators in the regulation of uterine leiomyoma growth.
pubmed:affiliation
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't