Felice Petraglia

Sphingosine 1-phosphate acts as proliferative and fibrotic cue in leiomyoma cells

To determine whether the bioactive sphingolipid sphingosine 1-phosphate (S1P) modulates cellular proliferation and synthesis of fibrotic proteins in leiomyoma differently than myometrial cells. A basic science study using human leiomyoma and myometrial cells. Not applicable. This is an in vitro study performed on cellular models. Leiomyoma and myometrial cells were treated with S1P, as well as with selective antagonists for S1P-specific G protein-coupled receptors and secondarily with inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and ezrin. The main outcome measures included cellular proliferation and fibrogenesis. Bromodeoxyuridine Cell Proliferation Assay was employed to measure deoxyribonucleic acid synthesis and proliferation, whereas western blot analysis was used to assess the expression of the fibrotic markers N-cadherin, α-smooth muscle actin, transgelin, and collagen type I alpha 1. Sphingosine 1-phosphate stimulates cellular proliferation of leiomyoma but not myometrial cells. The mitogenic effect elicited by S1P relies on the engagement of its specific receptor S1P These results, besides extending the knowledge on the molecular mechanism underlying uterine leiomyoma development and fibrosis, demonstrate the pathogenetic role of S1P in leiomyoma and support the rationale for targeting S1P signaling pathway as innovative potential treatment.

Recurrence of Uterine Fibroids After Conservative Surgery or Radiological Procedures: a Narrative Review

The present narrative review aims to discuss the available data on the incidence and the risk factors of uterine fibroids (UFs) recurrence after different types of conservative surgical or radiologic procedures in women wishing to preserve their uterus. UFs are the most common benign tumors in women all over the world. Clinical presentation, including abnormal uterine bleeding (AUB), pelvic pain, bulky symptoms, and infertility affect patients' quality of life, and a large variety of conservative treatments are available especially for those with desire of pregnancy. Fertility sparing surgery, by either laparoscopy, hysteroscopy or laparotomy, or radiological interventions (uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound), are the most common therapeutic approaches. However, the genetic or acquired predisposition to UFs remain despite the treatments, and the recurrences are frequently described in a large percentage of patients. The most relevant risk factors for recurrence of UFs are young age at the first surgery, incomplete fibroid resection, the presence of multiple lesions, an enlarged uterus, and the coexistence with other pelvic diseases. The discussion on the possible medical strategy to reduce the recurrence is an open field of clinical investigation, in particular by using hormonal drugs.