{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:09:27Z","timestamp":1782698967853,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T00:00:00Z","timestamp":1467158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Leiomyomas, monoclonal tumors developed by the transformation of myometrium somatic stem cells, are a major health concern that can severely impair quality of life. Pathological alterations of signaling pathways have been recognized as a key feature in a variety of human diseases. Our objective was to analyze treatment with all\u2010trans\u2010retinoic acid (ATRA) by suppression of the phosphoinositide 3\u2010kinase (PI3K) pathway on growth, signaling pattern and interactions among PI3K\/B\u2010cell lymphoma 2 (Bcl2)\/retinol leiomyoma proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cultures of paired myometrium and leiomyoma cells from premenopausal women undergoing hysterectomy were collected. Western blot and analysis of variance were used for analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant differences were detected between treatment with ATRA alone or with LY294002 (a PI3K growth suppressor) in response to treatment and among cell samples and cell numbers. Leiomyoma cells were less affected. Immunochemical analysis of signaling patterns demonstrated that treatments affected most of the examined protein levels differently. Significant differences between the cell type responses to treatment in pyruvate phosphate dikinase 1 (pPDK1), Bad and p\u03b2\u2010catenin levels were identified. The p\u03b2\u2010catenin level showed highly significant interaction between response to treatment and cell type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ATRA treatment on PI3K pathway suppression significantly affected growth, signaling pattern and interactions among PI3K\/Bcl2\/retinol proteins involved in the growth, survival and apoptosis of leiomyomas. Interpretation of our results suggests that increasing knowledge of the role of signaling interplay in the pathogenesis of leiomyomas may present an opportunity to use specific signal transduction inhibitors for treating and preventing this disorder.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jog.13068","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T17:57:54Z","timestamp":1467223074000},"page":"1343-1353","source":"Crossref","is-referenced-by-count":4,"title":["Targeting leiomyomas with all\u2010trans\u2010retinoic acid at phosphoinositide 3\u2010kinase pathway suppression: Effective roles of \u03b2\u2010catenin and of signaling interactions"],"prefix":"10.1111","volume":"42","author":[{"given":"Noa","family":"Friedman","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Hadassah Medical Center  Jerusalem Israel"},{"name":"Laboratory of Experimental Surgery Hadassah Medical Center  Jerusalem 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