Cell-Type Specific Actions of Progesterone Receptor Modulators in the Regulation of Uterine Leiomyoma Growth

Yoshida, Shigeki; Ohara, Noriyuki; Xu, Qin; Chen, Wei; Wang, Jiayin; Nakabayashi, Koji; Sasaki, Hidetada; Morikawa, Akira; Maruo, Takeshi

doi:10.1055/s-0030-1251483

Cited by 75 publications

(73 citation statements)

References 136 publications

(177 reference statements)

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“…Despite the limited knowledge about the specific events leading to the development of leiomyomas, they have been shown to represent hormone-sensitive tumors [2][3][4][5][6]. Case descriptions and studies originating from the late 1970s demonstrated that leiomyomas appear at the start of the reproductive age; they grow under the influence of sex steroids and regress following the menopause [7].…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Processes of apoptosis and cell proliferation in uterine myomas originating from reproductive and perimenopausal women

Plewka¹,

Plewka²,

Madej³

et al. 2011

Folia Histochem Cytobiol.

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P P P P Processes of apoptosis and cell proliferation in rocesses of apoptosis and cell proliferation in rocesses of apoptosis and cell proliferation in rocesses of apoptosis and cell proliferation in rocesses of apoptosis and cell proliferation in uterine myomas originating from uterine myomas originating from uterine myomas originating from uterine myomas originating from uterine myomas originating from reproductive and perimenopausal women reproductive and perimenopausal women reproductive and perimenopausal women reproductive and perimenopausal women reproductive and perimenopausal women We studied uterine myomas originating from females of reproductive age and from females of perimenopausal age. Uterine myomas represent benign tumors of the myometrium, and they develop frequently in women of reproductive age. The frequency of uterine myomas increases with age until women reach the menopause. The study included patients with a myomatous uterus, in the reproductive age or peri-menopausal age, independently evaluating small and large myomas. Myometrial alterations in their direct vicinity were evaluated independently of the myomas. The study included evaluation of immunolocalization of two index proteins which participate in myoma cells growth control: Ki-67 nuclear antigen and caspase 3. In women of reproductive age, both in small and large myomas, elevated immunostaining of Ki-67 was noted in parallel to low levels of caspase 3 staining, which indicated the ongoing process of proliferation. In women of peri-menopausal age with small or large myomas, no Ki-67 immunostaining was detected, while staining of caspase 3 manifested low levels. Proliferation in reproductive age women myomas is higher than in the peri-menopausal age. (Folia Histochemica et

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Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Processes of apoptosis and cell proliferation in uterine myomas originating from reproductive and perimenopausal women

Plewka¹,

Plewka²,

Madej³

et al. 2011

Folia Histochem Cytobiol.

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“…Поскольку прогес-терон -основной стимулятор роста миоматозных узлов, блокирование рецепторов к нему является патогенети-чески обоснованным путем уменьшения размеров опу-холи. Исследования на клеточных культурах продемон-стрировали антипролиферативные, антифибротические и проапоптотические эффекты УПА в отношении клеток лейомиомы и его нейтральность в отношении нормаль-ных клеток миометрия [18]. Кроме того, УПА оказывает ан-типролиферативное действие на эндометрий, что может объяснять его свойство индуцировать аменорею.…”

Section: подходы к медикаментозному лечению сочетанной патологии маткиunclassified

Concomitant endometriosis and leiomyoma in women of reproductive age

Zaporozhchenko

Сидоренко

Парубина

2017

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Endometriosis and leiomyoma commonly co-exist inside one uterus. Specialized surgical centers report detection frequency of comorbid endometriosis during surgery or laparoscopy that varies from 20 to 87% in patients with symptomatic fibroids.In authors practice the histological study of surgery samples from patients diagnosed with symptomatic fibroids (113 hysterectomies) revealed concomitant endometriosis in 26.5% cases.Clinical and morphological analysis showed that in patients with multiply fibroids, large volumes or submucous myomas comorbid adenomyosis doesn’t interfere significantly with the clinic course. But in cases of small-size solitary intramural or subserosis fibroids the clinic of symptomatic myomas is determined by the comorbid adenomyosis of diffuse-nodular or diffuse-lesion forms and 2–3 stages.Thus, endometriosis associated with leiomyomas causes more severe course of comorbidity. Patients with symptomatic fibroids are exposed to higher risk of endometriosis development, which must be kept in mind when planning the surgery treatment. Authors propose to enhance laparoscopic myomectomy with target revision of pelvis to reveal possible endometriosis, because laparoscopy provides the best opportunity to visualization of endometriosis lesions.The choice of pharmacotherapy of concomitant uterine pathology is limited. Gonadotropin-releasing hormone agonists is the only currently available group of drugs that labeled both for the treatment of endometriosis and fibroids. Selective progesterone-receptor modulator ulipristal acetate due to its unique antiproliferative and selective proapoptotic effect on the leiomyomas cellular component is very promising in the uterine-sparing therapy of myomas. In addition, it has pharmacodynamic effects on the endometrium, including antiproliferative effects that may contribute to the treatment of endometriosis. Clinical trial of ulipristal on this indication is ongoing (NCT02213081). For the present, in the absence of approved algorithms for the treatment of co-morbid pathology, the individual approach with combining preparations of different classes is relevant.

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“…www.endocrinology-journals.org including breast cancer, prostate cancer, cervical cancer, meningiomas, and leiomyosarcoma (Grunberg et al 1991, Spitz et al 2005, Engman et al 2008, Check et al 2010, Yoshida et al 2010. Additionally, it has potential use in different psychiatric disorders, including depression and Alzheimer's; however, in these diseases the antiglucocorticoid function seems to be more important (Benagiano et al 2008).…”

Section: Lanari Et Al: Antiprogestins In Breast Cancermentioning

confidence: 99%

Antiprogestins in breast cancer treatment: are we ready?

Lanari

Wargon²,

Rojas³

et al. 2012

Endocrine-Related Cancer

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Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. It is accepted that breast cancer is not a single disease, but instead constitutes a spectrum of tumor subtypes with distinct cellular origins, somatic changes, and etiologies. Molecular gene expression studies have divided breast cancer into several categories, i.e. basallike, ErbB2 enriched, normal breast-like (adipose tissue gene signature), luminal subtype A, luminal subtype B, and claudin-low. Chances are that as our knowledge increases, each of these types will also be subclassified. More than 66% of breast carcinomas express estrogen receptor alpha (ERa) and respond to antiestrogen therapies. Most of these ERC tumors also express progesterone receptors (PRs), the expression of which has been considered as a reliable marker of a functional ER. In this paper we will review the evidence suggesting that PRs are valid targets for breast cancer therapy. Experimental data suggest that both PR isoforms (A and B) have different roles in breast cancer cell growth, and antiprogestins have already been clinically used in patients who have failed to other therapies. We hypothesize that antiprogestin therapy may be suitable for patients with high levels of PR-A. This paper will go over the experimental evidence of our laboratory and others supporting the use of antiprogestins in selected breast cancer patients.

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Cell-Type Specific Actions of Progesterone Receptor Modulators in the Regulation of Uterine Leiomyoma Growth

Cited by 75 publications

References 136 publications

Processes of apoptosis and cell proliferation in uterine myomas originating from reproductive and perimenopausal women

Processes of apoptosis and cell proliferation in uterine myomas originating from reproductive and perimenopausal women

Concomitant endometriosis and leiomyoma in women of reproductive age

Antiprogestins in breast cancer treatment: are we ready?

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