Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones

Malik, Minnie; Britten, Joy; Cox, J.; Patel, Akash D; Catherino, William H.

doi:10.1016/j.fertnstert.2015.09.006

Cited by 26 publications

(18 citation statements)

References 71 publications

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“…Interestingly, the relevance of ECM in the growth of UL had been a matter of numerous studies and therapeutical approaches targeting ECM have been proposed repeatedly (e.g. [22–25]). Accordingly, future studies should address the possible influence of ECM presented in vitro and of three-dimensional cell cultures on the disappearance of MED12 -mutated cells.…”

Section: Discussionmentioning

confidence: 99%

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Factors affecting the loss of MED12-mutated leiomyoma cells during in vitro growth

et al. 2017

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Uterine leiomyomas (UL) are the most prevalent symptomatic human tumors at all and somatic mutations of the gene encoding mediator subcomplex 12 (MED12) constitute the most frequent driver mutations in UL. Recently, a rapid loss of mutated cells during in vitro growth of UL-derived cell cultures was reported, resulting in doubts about the benefits of UL-derived cell cultures. To evaluate if the rapid loss of MED12-mutated cells in UL cell cultures depends on in vitro passaging, we set up cell cultures from nine UL from 40–50 year old Caucasian patients with at least one UL. Cultured UL cells were investigated for loss of MED12-mutated cells. Genetic characterization of native tumor samples and adjacent myometrium was done by array analysis. “Aged” primary cultures without passaging were compared to cells of three subsequent passages. Comparative analyses of the mutated/non-mutated ratios between native tissue, primary cells, and cultured tumor cells revealed a clear decrease of MED12-mutated cells. None of the tumors showed gross alterations of the array profiles, excluding the presence of gross genomic imbalances besides the MED12 mutations as a reason for the intertumoral variation in the loss of MED12-mutated cells. Albeit at a lesser rate, loss of MED12-mutated cells from cell cultures of UL occurs even without passaging thus indicating the requirement of soluble factors or matrix components lacking in vitro. Identification of these factors can help to understand the mechanisms of the growth of the most frequent type of uterine leiomyomas and to decipher novel drug targets.

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Section: Discussionmentioning

confidence: 99%

“…In turn, these factors may be of relevance for in vivo growth thus representing possible therapeutic targets. Furthermore, three-dimensional cell cultures [22, 26, 27] may become a model system suitable to replace monolayer cultures if these latter type of culturing turns out better to support the growth of MED12 -mutated cells.…”

Section: Discussionmentioning

confidence: 99%

Factors affecting the loss of MED12-mutated leiomyoma cells during in vitro growth

et al. 2017

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“…A study revealed that the effect of sex hormone levels on patients with different ranges of hysterectomy was not statistically significant. However, after the total hysterectomy, the sex hormone levels were significantly lower than those before surgery [9].…”

Section: Introductionmentioning

confidence: 69%

High-throughput sequencing study of the effect of transabdominal hysterectomy on intestinal flora in patients with uterine fibroids

Wang

et al. 2020

BMC Microbiol

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Background: To investigate the effect of transabdominal hysterectomy on the diversity of the intestinal flora in patients with uterine fibroids. Patients with uterine fibroids were selected from stool specimens were collected from patients before and after surgery. Results: High-throughput sequencing of the 16S rRNA gene was used to detect the changes in microbial community structure and diversity, and the effects of total hysterectomy on the intestinal flora were further analyzed. Estrogen levels decreased after trans-abdominal hysterectomy. High-throughput sequencing showed that after abdominal hysterectomy, the abundance and diversity of the intestinal flora decreased. The abundance changes were mainly due to Proteobacteria, where their abundance increased. Conclusions: Trans-abdominal hysterectomy changes the intestinal flora of the body by lowering the level of estrogen in the body, which reduces the diversity and abundance of the intestinal flora.

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“…On a molecular level, GnRH agonists decrease the expression of factors important for fibroid growth to include Transforming Growth Factor-Beta, Epidermal Growth Factor, and Insulin-like Growth Factor. Further data from our laboratory has shown reduction of the extracellular components collagen -1, fibronectin, and versican with leuprolide acetate treatment [ 56 , 57 ].…”

Section: Gonadotropin-releasing Hormone Analogsmentioning

confidence: 99%

A Comprehensive Review of the Pharmacologic Management of Uterine Leiomyoma

Lewis

Malik

Britten

et al. 2018

BioMed Research International

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Uterine leiomyomata are the most common benign tumors of the gynecologic tract impacting up to 80% of women by 50 years of age. It is well established that these tumors are the leading cause for hysterectomy with an estimated total financial burden greater than $30 billion per year in the United States. However, for the woman who desires future fertility or is a poor surgical candidate, definitive management with hysterectomy is not an optimal management plan. Typical gynecologic symptoms of leiomyoma include infertility, abnormal uterine bleeding (AUB)/heavy menstrual bleeding (HMB) and/or intermenstrual bleeding (IMB) with resulting iron-deficiency anemia, pelvic pressure and pain, urinary incontinence, and dysmenorrhea. The morbidity caused by these tumors is directly attributable to increases in tumor burden. Interestingly, leiomyoma cells within a tumor do not rapidly proliferate, but rather the increase in tumor size is secondary to production of an excessive, stable, and aberrant extracellular matrix (ECM) made of disorganized collagens and proteoglycans. As a result, medical management should induce leiomyoma cells toward dissolution of the extracellular matrix, as well as halting or inhibiting cellular proliferation. Herein, we review the current literature regarding the medical management of uterine leiomyoma.

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Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones

Cited by 26 publications

References 71 publications

Factors affecting the loss of MED12-mutated leiomyoma cells during in vitro growth

Factors affecting the loss of MED12-mutated leiomyoma cells during in vitro growth

High-throughput sequencing study of the effect of transabdominal hysterectomy on intestinal flora in patients with uterine fibroids

A Comprehensive Review of the Pharmacologic Management of Uterine Leiomyoma

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