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Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjöld M, Gustafsson JA. The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. Kim S, Xu X, Hecht A, Boyer TG. Cell. Tanwar PS, Lee HJ, Zhang L, Zukerberg LR, Taketo MM, Rueda BR, Teixeira JM. Even if many risk factors suggested by epidemiologic studies have linked uterine leiomyomas to the e ects of estrogens and progesterone levels and their metabolism, other mechanisms may be involved in broids pathogenesis. Hum Pathol. Platelet-derived growth factor C is upregulated in human uterine fibroids and regulates uterine smooth muscle cell growth. Shynlova O, Dorogin A, Lye SJ. Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA. 1990;265:7709–12. Hum Reprod. Lee BS, Nowak RA. Endometriosis and uterine fibroids are important pathological conditions of the uterus.Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity and represents one of the most gynecological disorders affecting 10-15% of all women of reproductive age and >30% of … They are the most frequent indication for hysterectomy in the United States. 2003;3:281–92. Matrix Biol. Risk for estrogen-dependent diseases in relation to phthalate exposure and polymorphisms of CYP17A1 and estrogen receptor genes. Am J Obstet Gynecol. Fibroblast growth factors and their receptors: an information network controlling tissue growth, morphogenesis and repair. Brioso Rubio X, Beal SG, Ross JA, Kresak J. Acad Pathol. PLoS One. Kim JJ, Kurita T, Bulun SE. uterine tissues suggested that the role of sex steroid hormones in the pathophysiology of leiomyomas may be mediated by substances influencing the proliferation of smooth muscle cells and fibroblasts. J Biol Chem. Association between tumor necrosis factor α and uterine fibroids: A protocol of systematic review. J. 2001;169:79–86. Endocrinology. A mediator lost in the war on cancer. Pathogenesis and Medical Management of Uterine Fibroids: Amazon.de: Brosens, I. MED12 alterations in both human benign and malignant uterine soft tissue tumors. Efficacy and safety considerations in women with uterine leiomyomas treated with gonadotropin-releasing hormone agonists: the estrogen threshold hypothesis. The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. Fibroids are made of muscle cells and other tissues that grow in and around the wall of the uterus, or womb. Kimura F, Tsuji S and Murakami T (2018) Molecular Pathogenesis of Uterine Fibroids Uterine Fibroids and Adenomyosis, 10.1007/978-981-10-7167-6_3, (37-57), . J Clin Endocrinol Metab. Targeting HIF-1 for cancer therapy. Membrane progesterone receptor expression in mammalian tissues: a review of regulation and physiological implications. Mol Interv. 2006;21:1869–77. Uterine artery embolization aims to cause infarction of fibroids throughout the uterus while preserving normal uterine tissue. Researchers investigated aberrant gene expression in uterine fibroids to elucidate their molecular pathogenesis. Biol Reprod. Lab Investig. Purpose of review: Uterine leiomyoma (fibroids) is a gynecologic disorder impacting the majority of women in the United States. Chegini N, Luo X, Ding L, Ripley D. The expression of Smads and transforming growth factor beta receptors in leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy. Steroid hormones and leiomyomas. 1998;394:485–90. Markowski DN, Helmke BM, Belge G, Nimzyk R, Bartnitzke S, Deichert U, Bullerdiek J. HMGA2 and p14Arf: major roles in cellular senescence of fibroids and therapeutic implications. Copyright © 2015 Elsevier Ltd. All rights reserved. Gentry CC, Okolo SO, Fong LF, Crow JC, Maclean AB, Perrett CW. Progesterone receptor A and B protein expression in human breast cancer. Cancer Res. Gynecol Endocrinol. 2003;209:9–16. Progesterone action is … 2011;334:252–5. Van der Ven LT, Roholl PJ, Gloudemans T, Van Buul-Offers SC, Welters MJ, Bladergroen BA, Faber JA, Sussenbach JS, Den Otter W. Expression of insulin-like growth factors (IGFs), their receptors and IGF binding protein-3 in normal, benign and malignant smooth muscle tissues. Tian R, Wang Z, Shi Z, Li D, Wang Y, Zhu Y, Lin W, Gui Y, Zheng XL. 1990;9:1603–14. Ren Y, Yin H, Tian R, Cui L, Zhu Y, Lin W, Tang XD, Gui Y, Zheng XL. Uterine fibroids (also called leiomyomas) are growths made up of the muscle and connective tissue from the wall of the uterus. PLoS One. Kasai T, Shozu M, Murakami K, Segawa T, Shinohara K, Nomura K, Inoue M. Increased expression of type I 17beta-hydroxysteroid dehydrogenase enhances in situ production of estradiol in uterine leiomyoma. 2005;90:5349–55. Development. 1991;266:11947–54. 2002;84:431–6. Mol Biol Int. Deng W, Feng X, Li X, Wang D, Sun L. Hypoxia-inducible factor 1 in autoimmune diseases. Menasce LP, White GR, Harrison CJ, Boyle JM. 2000;65:585–92. 2015;66:271–80. Szotek PP, Chang HL, Zhang L, Preffer F, Dombkowski D, Donahoe PK, Teixeira J. 2011;12:9–22. 2011;76:11–7. J Clin Endocrinol Metab. The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. Ono M, Qiang W, Serna VA, Yin P, Coon JS V, Navarro A, Monsivais D, Kakinuma T, Dyson M, Druschitz S, Unno K, Kurita T, Bulun SE. Reprod Sci. Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P. Two distinct estrogen regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 2013;42:535–42. Cell. Epub 2010 Apr 22. Expression profiling of uterine leiomyomata cytogenetic subgroups reveals distinct signatures in matched myometrium: transcriptional profiling of the t(12;14) and evidence in support of predisposing genetic heterogeneity. Ciarmela P, Islam MS, Reis FM, Gray PC, Bloise E, Petraglia F, Vale W, Castellucci M. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. J Biol Chem. 2002;8:1071–8. Kawaguchi K, Fujii S, Konishi I, Nanbu Y, Nonogaki H, Mori T. Mitotic activity in uterine leiomyomas during the menstrual cycle. Endocrinology. Proc Natl Acad Sci U S A. Figure 1. 2010;662:399–405. 1997;76:245–55. 2013;34:130–62. Matsuo H, Kurachi O, Shimomura Y, Samoto T, Maruo T. Molecular bases for the actions of ovarian sex steroids in the regulation of proliferation and apoptosis of human uterine leiomyoma. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Levin ER. ; Evdokimova, D.V. Mol Cell Biol. A Method for Counting, This patient FAQ explains what uterine fibroids are, as well as diagnosis and treatment options. 2011;4:134–46. mTOR signaling confers resistance to targeted cancer drugs. 2002;172:83–93. Hum Reprod Update. The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. Oncogene. 2007;303:536–48. Barbarisi A, Petillo O, Di Lieto A, Melone MA, Margarucci S, Cannas M, Peluso G. 17-beta estradiol elicits an autocrine leiomyoma cell proliferation: evidence for a stimulation of protein kinase-dependent pathway. Courtnay R, Ngo DC, Malik N, Ververis K, Tortorella SM, Karagiannis TC. Presence of epidermal growth factor, platelet-derived growth factor, and their receptors in human myometrial tissue and smooth muscle cells: their action in smooth muscle cells in vitro. Fibroids are quite common, impacting up to 70% of women by the age of 50. Pérot G, Croce S, Ribeiro A, et al. 2020 Dec 5;9(12):3948. doi: 10.3390/jcm9123948. Tumors occur in ∼77% of women overall and are clinically manifest in ∼25% by age 45 years. Mol Biol Rep. 2015;42:841–51. J Steroid Biochem Mol Biol. Uterine fibroids (UFs; also known as leiomyomas) are the most common benign neoplastic threat to women's health in U.S. and worldwide, with annual health care costs estimated in the hundreds of billions of dollars. Immunohistochemical localization of growth factors and their receptors in uterine leiomyomas and matched myometrium. 1993;8:1796–806. Mayer A, Hoeckel M, von Wallbrunn A, Horn LC, Wree A, Vaupel P. HIF-mediated hypoxic response is missing in severely hypoxic uterine leiomyomas. 2008;69:462–70. Markowski DN, Bartnitzke S, Löning T, Drieschner N, Helmke BM, Bullerdiek J. MED12 mutations in uterine fibroids—their relationship to cytogenetic subgroups. Adult mouse myometrial label-retaining cells divide in response to gonadotropin stimulation. Insulin-like growth factor (IGF), IGF binding protein (IGFBP), and IGF receptor gene expression and IGFBP synthesis in human uterine leiomyomata. Uterine smooth muscle cells express functional receptors (flt-1 and KDR) for vascular permeability factor/vascular endothelial growth factor. Ikushima H, Miyazono K. TGFbeta signalling: a complex web in cancer progression. Transforming growth factor-beta3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Guri Y, Hall MN. Flow chart of the proposed WSN. Int J Oncol. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. 2002;398:284–90. Biol Reprod. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. 1995;80:1853–8. eCollection 2020 Jan-Dec. Chen R, Su Z, Yang L, Xin L, Yuan X, Wang Y. BMC Surg. Role of transforming growth factor Beta in human cancer. Certain signs … Kovacs KA, Oszter A, Gocze PM, Kornyei JL, Szabo I. Expression of the CYP19 gene and its product aromatase cytochrome P450 in human uterine leiomyoma tissues and cells in culture. Ding L, Xu J, Luo X, Chegini N. Gonadotropin releasing hormone and transforming growth factor beta activate mitogen-activated protein kinase/extracellularly regulated kinase and differentially regulate fibronectin, type I collagen, and plasminogen activator inhibitor-1 expression in leiomyoma and myometrial smooth muscle cells. 2015;2015:538019. Sant'Anna GDS, Brum IS, Branchini G, Pizzolato LS, Capp E, Corleta HVE. J Biochem. Morikawa M, Derynck R, Miyazono K. TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology. 1996;81:3222–30. Obstet Gynecol. Uterine fibroid, also called uterine leiomyomata or uterine myoma, benign tumour that originates from the smooth muscle wall of the uterus and may be single but usually occurs in clusters. 2004;20:781–810. Harrison-Woolrych ML, Sharkey AM, Charnock-Jones DS, Smith SK. Dechering K, Boersma C, Mosselman S. Estrogen receptors alpha and beta: two receptors of a kind. They contain a large amount of extracellular matrix (including collagen, … Pathogenesis of uterine leiomyomas . Researchers investigated aberrant gene expression in uterine fibroids to elucidate their molecular pathogenesis. Endocrinology. Sanci M, Dikis C, Inan S, Turkoz E, Dicle N, Ispahi C. Immunolocalization of VEGF, VEGF receptors, EGF-R and Ki-67 in leiomyoma, cellular leiomyoma and leiomyosarcoma. Exp Mol Med. Different effects of epidermal growth factor on smooth muscle cells derived from human myometrium and from leiomyoma. UFs may cause various clinical issues which might constitute the major reason of the overall deterioration of the quality of life. Peng Y, Laser J, Shi G, et al. Would you like email updates of new search results? The aim of this review is to summarize recent human and experimental … The pathogenesis of uterine leiomyomas is reviewed here. The uterus is a pear-shaped organ composed of the body of the uterus on top and the cervix below, which connects at its lower end to the vagina. In this overview of the etiology and pathogenesis of uterine fibroids, we have attempted to analyze the literature and present prevailing evidence and opinions. Antiproliferative effects by Let-7 repression of high-mobility group A2 in uterine leiomyoma. This is a preview of subscription content. Nat Rev Cancer. J Clin Endocrinol Metab. 1990;163:1114–9. Leiomyomas are benign uterine tumors of unknown aetiology. Uterine fibroids are non-cancerous tumors that develop in the muscle of the uterus. Lab Investig. Shimomura Y, Matsuo H, Samoto T, Maruo T. Up-regulation by progesterone of proliferating cell nuclear antigen and epidermal growth factor expression in human uterine leiomyoma. 2014 Sep;102(3):630-9. doi: 10.1016/j.fertnstert.2014.07.1238. 1-3 They may be asymptomatic or cause a range of severe and chronic symptoms. Huang PC, Li WF, Liao PC, Sun CW, Tsai EM, Wang SL. Whole exome sequencing in a random sample of North American women with leiomyomas identifies MED12 mutations in majority of uterine leiomyomas. Obstet Gynecol. 2006;88:141–6. Overexpression of the Wnt5b gene in leiomyoma cells: implications for a role of the Wnt signaling pathway in the uterine benign tumor. 1972;40:479–86. Uterine leiomyomas, or fibroids, represent a major public health problem. 2013;8:e66632. Many women with fibroids have no symptoms. J Biol Chem. 2007;25:1317–25. Transforming growth factor beta3 regulates the versican variants in the extracellular matrix-rich uterine leiomyomas. The role of sex steroids is critical for leiomyoma development and maintenance, but a number of autocrine and paracrine messengers are involved in this process; hence, numerous pathways remain to be explored in therapeutic innovations for treating this common disease. Rauk PN, Surti U, Roberts JM, Michalopoulos G. Mitogenic effect of basic fibroblast growth factor and estradiol on cultured human myometrial and leiomyoma cells. Rossi MJ, Chegini N, Masterson BJ. Future research should map specific pathways of hormone action in fibroids. J Clin Endocrinol Metab. Estradiol and progesterone induce mature leiomyoma cells to release mitogenic stimuli to adjacent immature cells, thereby providing uterine leiomyoma with undifferentiated cells that are likely to support tumor growth. J Clin Med. 2017 Aug;33(8):629-633. doi: 10.1080/09513590.2017.1301924. Biol Reprod. Maruo T, Matsuo H, Shimomura Y, Kurachi O, Gao Z, Nakago S, Yamada T, Chen W, Wang J. The pathogenesis of leiomyomas is not well understood. Uterine fibroids are the most common benign tumors in women of childbearing age. They are benign monoclonal tumors arising from the smooth muscle cells of the myometrium. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. 1999;57(Suppl 2):49–58. Pambuccian CA, Oprea GM, Lakatua DJ. Pathogenesis of Uterine Leiomyoma.. Risk Factors. Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Comparative analysis of cyclin D1 and oestrogen receptor (alpha and beta) levels in human leiomyoma and adjacent myometrium. Dysregulation of IGF-I signaling in uterine leiomyoma. Arch Biochem Biophys. Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, et al. … 1999;276:E1112–8. Am J Phys. Estradiol and progesterone induce mature leiomyoma cells to release mitogenic stimuli to adjacent immature cells, thereby providing uterine leiomyoma with undifferentiated cells that are likely to support tumor growth. 2008;135(6):1013. Wang J, Ohara N, Takekida S, Xu Q, Maruo T. Comparative effects of heparin-binding epidermal growth factor-like growth factor on the growth of cultured human uterine leiomyoma cells and myometrial cells. Paracrine activation of WNT/beta-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Am J Obstet Gynecol. Prog Growth Factor Res. J Clin Oncol. 2007;104:18700–5. 1990;27:93–101. Fibroid growth and medical options for treatment. Quantification of vascular endothelial growth factor-A in leiomyomas and adjacent myometrium. When symptomatic, these noncancerous tumors can cause severe morbidity including pelvic pain, menorrhagia, and infertility. Am J Obstet Gynecol. Noman MZ, Hasmim M, Messai Y, Terry S, Kieda C, Janji B, Chouaib S. Hypoxia: a key player in antitumor immune response. The selective estrogen receptor modulator (SERM) raloxifene and the selective PR modulators (SPRMs) mifepristone, asoprisnil, and ulipristal acetate have been shown in clinical trials to inhibit fibroid growth. The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. Complex networks of multiple factors such as growth factors and WNT/β-catenin signaling have been shown to be involved in the pathogenesis of uterine fibroids. Bulun SE, Simpson ER, Word RA. Cite as. Novel actions of estrogen to promote proliferation: integration of cytoplasmic and nuclear pathways. 1986;320:695–9. Bulun SE. Matsumura A, Kubota T, Taiyoh H, Fujiwara H, Okamoto K, Ichikawa D, Shiozaki A, Komatsu S, Nakanishi M, Kuriu Y, Murayama Y, Ikoma H, Ochiai T, Kokuba Y, Nakamura T, Matsumoto K, Otsuji E. HGF regulates VEGF expression via the c-Met receptor downstream pathways, PI3K/Akt, MAPK and STAT3, in CT26 murine cells. Protopapas A, Grimbizis G, Athanasiou S, Loutradis D. Facts Views Vis Obgyn. Estrogen signaling: a subtle balance between ER alpha and ER beta. Maruo T, Ohara N, Wang J, Matsuo H. Sex steroidal regulation of uterine leiomyoma growth and apoptosis. is generating new treatment strategies. CONCLUSIONS: Loss of expression of CB1, FAAH, GPR55, and PEA production are linked to the pathogenesis of uterine fibroids and further understanding of this might eventually lead to better disease indicators or the development of therapeutic potentials that might eventually be used in the management of uterine fibroids. Uterine fibroids. They may occur in more than 70% of women, and ~25% of women show clinically significant lesions ( Buttram and Reiter, 1981 ; Cramer and Patel, 1990 ). The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. On the surgical front, uterine artery embolization. Genomics. J Biol Chem. 2005;308:1589–92. 1989;74:856–62. Localization of the estrogen receptor locus(ESR) to chromosome 6q25.1 by FISH and a simple post-FISH banding technique. 2008;6:663–73. Environ Sci Pollut Res Int. Mol Cancer Res. Hum Reprod. 2002;22:7004–701. 2006;74:839–49. 2011;31:753–61. In Vivo. 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