Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells

Xu, Qin; Ohara, Noriyuki; Chen, Wei; Liu, Jin; Sasaki, Hidetada; Morikawa, Akira; Sitruk-Ware, Régine; Johansson, Elof D. B.; Maruo, Takeshi

doi:10.1093/humrep/del159

Cited by 88 publications

(67 citation statements)

References 36 publications

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“…It was demonstrated that VEGF is necessary for the growth of leiomyoma xenografts in vivo (104). VEGF represents a potential therapeutic target in leiomyoma, and Xu and colleagues demonstrated that it is downregulated by the selective progesterone receptor modulator CDB-2914 (105).…”

Section: Role Of Individual Growth Factors In Leiomyoma Pathobiologymentioning

confidence: 99%

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Borahay

Al-Hendy

Kılıç

et al. 2015

Mol Med

129

147

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Uterine leiomyomas are the most common tumors of the female genital tract, affecting 50% to 70% of females by the age of 50. Despite their prevalence and enormous medical and economic impact, no effective medical treatment is currently available. This is, in part, due to the poor understanding of their underlying pathobiology. Although they are thought to start as a clonal proliferation of a single myometrial smooth muscle cell, these early cytogenetic alterations are considered insufficient for tumor development and additional complex signaling pathway alterations are crucial. These include steroids, growth factors, transforming growth factor-beta (TGF-β)/Smad; wingless-type (Wnt)/β-catenin, retinoic acid, vitamin D, and peroxisome proliferator-activated receptor γ (PPARγ). An important finding is that several of these pathways converge in a summative way. For example, mitogen-activated protein kinase (MAPK) and Akt pathways seem to act as signal integrators, incorporating input from several signaling pathways, including growth factors, estrogen and vitamin D. This underlines the multifactorial origin and complex nature of these tumors. In this review, we aim to dissect these pathways and discuss their interconnections, aberrations and role in leiomyoma pathobiology. We also aim to identify potential targets for development of novel therapeutics.

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Section: Role Of Individual Growth Factors In Leiomyoma Pathobiologymentioning

confidence: 99%

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Borahay

Al-Hendy

Kılıç

et al. 2015

Mol Med

129

147

View full text Add to dashboard Cite

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“…This action of VA 2914 was not observed in the surrounding normal myometrial cells, suggesting a cell type specific action of this SPRM on leiomyoma cells [68].…”

Section: Treatment Of Uterine Leiomyomatamentioning

confidence: 82%

Gynaecological uses of a new class of steroids: the selective progesterone receptor modulators

Pintiaux

Chabbert-Buffet

Foidart

2009

Gynecological Endocrinology

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“…Although it is structurally similar to mifepristone, ulipristal has less antiglucocorticoid activity providing a potential advantage for long term use. Unlike RU 486 which affected both leiomyoma and myometrial cells, UPA and asoprisnil affected only leiomyomata growth along with expression of growth factors, cytokines and proteases like MMP along with downregulating Bcl2 and upregulating caspase [37][38][39] . Levens et al evaluated the effect of 10 mg and 20 mg, CDB2914 administered 3 months in women with symptomatic fibroids in a randomized placebo controlled trials.…”

Section: Role Of Ulipristal Acetatementioning

confidence: 93%

Medical Management of leipmyomas-emphasis for different geographical regions

KocharKaur¹

2015

JGNB

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Leiomyomas are the common benign tumours of uterus. Surgery is the most common mode of treatment of symptomatic fibroids. With the advent of minimally invasive interventional procedures like uterine artery embolization (UAE), and focused ultrasound on MRI we got some lesser invasive techniques, although they have drawbacks regarding ovarian reserve etc for patients desiring fertility. Initially GnRH agonists like leuprolide acetate were the most effective medical agents introduced, but their drawback was bone density demineralization, hot flushes on long term use besides cost. Selective progesterone receptor modulators gradually got introduced with initial trials with mifepristone (RU486), followed by asoprisnil, ulipristalacetate. Since mifepristone had antiglucocorticoid and androgen receptor activity it was not approved by FDA for license, while four PEARL trials have got completed for UPA acetate 5&10mg regarding safety and efficacy and intermittent therapy with 5mg got FDA approval in Europe and Canada before surgery. Further trials indicated it may be the future drug of choice for patients desiring fertility for long term intermittent therapy and possibly avoiding surgery and its complications like adhesions, uterine scar and risk for rupture during pregnancy. However in countries where uripristal is not available still one is forced to use mifepristone. Detailed mechanism of all these drugs is discussed and a case report of a young unmarried girl with high BMI is reported where mifepristone intermittent was effective not only in relieving patients symptoms but effective in decreasing uterine and fibroid volume which highlights how in such young cases one can preserve future fertility without putting them at risk of surgery and sometimes myomectomy complications ending in hysterectomy.

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Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells

Abstract: These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner.

Cited by 88 publications

References 36 publications

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Gynaecological uses of a new class of steroids: the selective progesterone receptor modulators

Medical Management of leipmyomas-emphasis for different geographical regions

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