The association between childbirth, breastfeeding, and uterine fibroids: an observational study.

The aim of this study was to investigate the effect of childbirth and breastfeeding on uterine fibroids and to identify the factors associated with size variations. This was a monocenter observational study carried on women with a sonographic diagnosis of uterine fibroids from January 2007 to December 2016, with no indication for immediate treatment, and who became pregnant within one year from diagnosis. All patients were re-evaluated six months after delivery. Fibroid diameters were compared between pre-pregnancy period, first, second, third trimester and post-delivery. The rate of "regressed" (growth of diameter <-40%), "unchanged" (growth of diameter between -40% and +40%) or "increased" (growth of diameter >+40%) fibroids at the post-delivery evaluation with respect to the pre-pregnancy state was calculated. One-hundred fifty-seven women were included in the final analysis. At the post-delivery ultrasound, a significant reduction of the fibroid diameter with respect to all previous examinations was observed, and there was no evidence of 67 (37.2%) fibroids. Ongoing breastfeeding was positively associated with an "unchanged" or "regressed" fibroid diameter (adOR 3.23, 95%CI: 1.35-7.70, p < 0.01). Smaller pre-gravidic fibroids were more likely to return to pre-pregnancy dimensions or to regress, with a cut-off of 32 mm for lactating women and of 26 mm for non-lactating women. In conclusion, fibroids seem to return to pre-pregnancy dimensions or to regress in the post-partum period. This process may be sustained by uterine involution and hormonal variations, with an additional role of breastfeeding.

A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune interaction.

Nm23-H1 is a metastasis suppressor gene whose overexpression is associated with both reduced cell motility in various cancers and increased metastatic potential in neuroblastomas, osteosarcomas, and hematological malignances. We previously reported that Nm23-H1 exerts tumor suppressor action in prostate cancer cells and that h-Prune, which is overexpressed in various tumor types, binds Nm23-H1. Moreover, blockage of the Nm23-H1/h-Prune interaction with a competitive permeable peptide (CPP) attenuates migration of breast and neuroblastoma cells. This series of events suggests that the Nm23-H1/h-Prune protein complex regulates cancer progression and that its specific impairment could be a new therapeutic strategy in oncology. We found that CPP leads to inhibition of the AKT/mTORv and NF-kBv signaling pathways and also activates apoptosis. To obtain a proof-of-concept of our hypothesis, we used a xenograft model of prostate cancer to evaluate whether impairment of this complex using CPP results in an anti-tumoral effect. Using a mouse orthotopic model with bioluminescent imaging, we show evidences that CPP reduces prostate cancer metastases formation. In conclusion, CPP being able to impair formation of the h-Prune/Nm23-H1 complex holds promise for the treatment of prostate cancer.

H-Prune through GSK-3ß interaction sustains canonical WNT/ß-catenin signaling enhancing cancer progression in NSCLC.

H-Prune hydrolyzes short-chain polyphosphates (PPase activity) together with an hitherto cAMP-phosphodiesterase (PDE), the latest influencing different human cancers by its overexpression. H-Prune promotes cell migration in cooperation with glycogen synthase kinase-3 (Gsk-3ß). Gsk-3ß is a negative regulator of canonical WNT/ß-catenin signaling. Here, we investigate the role of Gsk-3ß/h-Prune complex in the regulation of WNT/ß-catenin signaling, demonstrating the h-Prune capability to activate WNT signaling also in a paracrine manner, through Wnt3a secretion. In vivo study demonstrates that h-Prune silencing inhibits lung metastasis formation, increasing mouse survival. We assessed h-Prune levels in peripheral blood of lung cancer patients using ELISA assay, showing that h-Prune is an early diagnostic marker for lung cancer. Our study dissects out the mechanism of action of h-Prune in tumorigenic cells and also sheds light on the identification of a new therapeutic target in non-small-cell lung cancer.