Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.

Alcoholism is associated with breast cancer incidence and progression, and moderate chronic consumption of ethanol is a risk factor. The mechanisms involved in alcohol's oncogenic effects are unknown, but it has been speculated that they may be mediated by acetaldehyde. We used the immortalized normal human epithelial breast cell line MCF-12A to determine whether short- or long-term exposure to ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations, induces their oncogenic transformation and/or the acquisition of epithelial mesenchymal transition (EMT).

Separate or combined treatments with daily sildenafil, molsidomine, or muscle-derived stem cells prevent erectile dysfunction in a rat model of cavernosal nerve damage.

Introduction: Long-term daily administration of phosphodiesterase type 5 (PDE5) inhibitors in the rat prevents or reverses corporal veno-occlusive dysfunction (CVOD) and smooth muscle cell (CSMC) loss and fibrosis, in both aging and bilateral cavernosal nerve resection (BCNR) models for erectile dysfunction. In the aging rat model, corporal implantation of skeletal muscle-derived stem cells (MDSC) reverses CVOD. Nitric oxide (NO) and cyclic guanosine monophosphate can modulate stem cell lineage.

Effects of sildenafil and/or muscle derived stem cells on myocardial infarction.

Background: Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i) counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal muscle-derived stem cells (MDSC) exerts some of these effects. PDE5i and stem cells in combination were found to be more effective in non-MI cardiac repair than each treatment separately. We have now investigated whether sildenafil at lower doses and MDSC, alone or in combination are effective to attenuate LV remodeling after MI in rats.

Treatment of Peyronie's disease with PDE5 inhibitors: an antifibrotic strategy.

Peyronie's disease (PD) is a localized fibrotic condition of the tunica albuginea that is associated with risk factors for corpora cavernosa fibrosis (such as advanced age and diabetes) and Dupuytren contracture, another localized fibrotic process. Most of the current pharmacological treatments for PD are not based on antifibrotic approaches that have shown promising results in animal models and clinical efficacy in other fibrotic conditions, which may explain why they are generally unsuccessful. Evidence gathered in human specimens and animal models of PD have elucidated aspects of its etiology and histopathology, showing that overexpression of transforming growth factor beta1, plasminogen activator inhibitor 1, reactive oxygen species and other profibrotic factors, which are, in most cases, assumed to be induced by trauma to the tunica albuginea, leads to myofibroblast accumulation and excessive deposition of collagen.

Diabetes-relevant regulation of cultured blood outgrowth endothelial cells.

Many cell and tissue abnormalities in diabetes mellitus are mediated by auto- and paracrine TGFbeta which is induced by high ambient glucose and glycated proteins. In most cell types TGFbeta reduces cell proliferation and enhances apoptosis which are mediated through the TGFbeta type I receptor, Alk5. In contrast, early diabetic microangiopathy is characterized by endothelial cell proliferation.

Mechanisms of penile fibrosis.

Introduction: Penile fibrosis has been conceptually identified with the plaque that develops in the tunica albuginea in Peyronie's disease (PD), or with localized processes induced in the corpora cavernosa by ischemic or traumatic events. Recently, it has been proposed that a diffuse, progressive, and milder intracorporal fibrosis, which affects also the media of the penile arteries, is responsible for vasculogenic erectile dysfunction (ED) associated with aging, smoking, diabetes, hypertension, and post-radical prostatectomy. These processes differ in etiology, time course, target cells, and treatment, but have many features in common.