ERß- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis.

In endometriosis, stromal and epithelial cells from the endometrium form extrauterine lesions and persist in response to estrogen (E2) and prostaglandin E2 (PGE2). Stromal cells produce excessive quantities of estrogen and PGE2 in a feed-forward manner. However, it is unknown how estrogen stimulates cell proliferation and survival for the establishment and persistence of disease. Previous studies suggest that estrogen receptor-ß (ERß) is strikingly overexpressed in endometriotic stromal cells. Thus, we integrated genome-wide ERß binding data from previously published studies in breast cells and gene expression profiles in human endometriosis and endometrial tissues (total sample number = 81) and identified Ras-like, estrogen-regulated, growth inhibitor (RERG) as an ERß target. Estradiol potently induced RERG mRNA and protein levels in primary endometriotic stromal cells. Chromatin immunoprecipitation demonstrated E2-induced enrichment of ERß at the RERG promoter region. PGE2 via protein kinase A phosphorylated RERG and enhanced the nuclear translocation of RERG. RERG induced the proliferation of primary endometriotic cells. Overall, we demonstrated that E2/ERß and PGE2 integrate at RERG, leading to increased endometriotic cell proliferation and represents a novel candidate for therapeutic intervention.

Ligand-activated peroxisome proliferator-activated receptor ß/δ modulates human endometrial cancer cell survival.

Endometrial cancer is the fourth most common malignancy among women and is a major cause of morbidity contributing to approximately 8,200 annual deaths in the USA. Despite advances to the understanding of endometrial cancer, novel interventions for the disease are necessary given that many tumors become refractory to therapy. As a strategy to identify novel therapies for endometrial carcinoma, in this study, we examined the contribution of the peroxisome proliferator-activated receptor ß/δ (PPARß/δ) to endometrial cancer cell proliferation and apoptosis. We found that when activated with the highly selective PPARß/δ agonists, GW0742 and GW501516, PPARß/δ inhibited the proliferation and markedly induced the apoptosis of three endometrial cancer cell lines. The specificity of the PPARß/δ-induced effects on cell proliferation and apoptosis was demonstrated using PPARß/δ-selective antagonists and PPARß/δ small interfering RNA in combination with PPARß/δ-selective agonists. Furthermore, we showed that PPARß/δ activation increased phosphatase and tensin homolog expression, which led to protein kinase B (AKT) and glycogen synthase kinase-3ß (GSK3ß) dephosphorylation, and increased ß-catenin phosphorylation associated with its degradation. Overall, our data suggest that the antitumorigenic effect of PPARß/δ activation in endometrial cancer is mediated through the negative regulation of the AKT/GSK3ß/ß-catenin pathway. These findings warrant further investigation of PPARß/δ as a therapeutic target in endometrial cancer.

Use and perceptions of antibiotics for upper respiratory infections among college students.

BACKGROUND: Upper respiratory infections (URIs) are mainly viral in nature, rendering antibiotics ineffective. Little is known about what college students believe concerning the effectiveness of antibiotics as a treatment for URIs. METHODS: Students (n=425) on 3 college campuses were surveyed using a survey describing 3 variations in presentation of an uncomplicated URI. Participants were questioned about their likelihood of using a variety of treatments for the URI and about their likelihood of seeking a physician's care. RESULTS: The percentage of students endorsing antibiotic use differed significantly by symptom complex. Likelihood of seeking medical care also differed significantly across symptom groups, with greater endorsement in the discolored nasal discharge and low-grade fever scenarios. Stepwise multiple regression analysis revealed that belief in antibiotic effectiveness for cold symptoms decreased with tic and Therapeutic increasing years of higher education. Likelihood of antibiotic use across different scenarios increased with age. Likelihood of seeking care across different scenarios was related to type of health insurance and belief in antibiotic effectiveness. CONCLUSIONS: Undergraduate college students show poor recognition of typical presentations of the common cold and have misconceptions about effective treatment. Although increasing years of college correlated with decreasing belief in antibiotics' effectiveness for a cold, more health education at the college level is recommended.

Acrochordon, diabetes and associations.

A study of clinical profile of acrochordons was carried out in 100 patients. Their association with diabetes mellitus and other disorders was studied. Acrochordons were found to be closely associated with pseudo-acanthosis nigricans, seborrhoeic keratosis, obesity and non-insulin dependent diabetes mellitus.

Ciprofloxacin therapy in chronic folliculitis of legs.

The efficacy of ciprofloxacin was evaluated in 25 patients with chronic folliculitis of legs in a double-blind cross over study. Though ciprofloxacin was found to be far more effective than the placebo the average remission time was only 44.5 days.