GPER-induced signaling is essential for the survival of breast cancer stem cells

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER⁻/PR⁺ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.     

Predictive factors of positive online patient ratings of spine surgeons

BACKGROUND

Online physician rating websites are increasingly used by patients to evaluate their doctors. The purpose of this investigation was to evaluate factors associated with better spine surgeon ratings.

Anejaculation: Relevance to Sexual Enjoyment in Men and Women

IntroductionEjaculation and orgasm are important components of sexual response in men. Our understanding of both phenomena is limited. Anejaculation can be a source of substantial distress, even when procreation (ostensibly the only purpose of ejaculation itself) is not a priority.AimTo present an opinion on male perceptions of ejaculation disorders (specifically anejaculation) based on a variety of data sources, including peer-reviewed literature.MethodsA non-systematic review of literature on anejaculation and other impairments of ejaculatory and orgasmic response was conducted. Relevant articles were critically analyzed and reportedMain Outcome MeasureAn opinion is presented, based on existing data sources, on how and why ejaculation is deemed important to men and their sexual partners.ResultsThe peer-reviewed literature on disorders of ejaculation is scant; existing reports oftentimes do not adequately distinguish between orgasm and ejaculation in assessment. Men’s perceptions of ejaculation quality appear to be positively associated with satisfaction with sexual response, particularly regarding orgasm. Based on very limited data, female sexual partners of men appear to often (but not always) value the orgasmic experience of their partner; only a minority prioritize actual ejaculation. There is evidence that disorders of ejaculation may be particularly troublesome for men who have sex with men.Clinical ImplicationsThe influence of medical conditions and treatments on ejaculation should be considered in the clinical context. Psychological adaptations and interventions may be of value in some cases.Strengths & LimitationsData on the clinical relevance of anejaculation outside the context of concomitant orgasmic dysfunction are sparse. Men’s experience of orgasm is at least partially associated with ejaculation-specific variables; whether this association is mediated by psychological, physical, or a combination of factors remains unclear.ConclusionsEjaculation, orgasm, and sexual satisfaction are closely intertwined but distinct phenomena.Shindel AW. Anejaculation: Relevance to Sexual Enjoyment in Men and Women. J Sex Med 2019;16:1324–1327.