RESUMEN
Prostate cancer (PCa) is the second leading cause of male cancer-related deaths in the United States. The pre-mature forms of prostate-specific antigen (PSA), proPSA, were shown to be associated with PCa. However, there is a technical challenge in the development of antibody-based immunoassays for specific recognition of each individual proPSA isoform. Herein, we report the development of highly specific, antibody-free, targeted mass spectrometry assays for simultaneous quantification of [-2], [-4], [-5], and [-7] proPSA isoforms in voided urine. The newly developed proPSA assays capitalize on Lys-C digestion to generate surrogate peptides with appropriate length (9-16 amino acids) along with long-gradient liquid chromatography separation. The assay utility of these isoform markers was evaluated in a cohort of 30 well-established clinical urine samples for distinguishing PCa patients from healthy controls. Under the 95% confidence interval, the combination of [-2] and [-4] proPSA isoforms yields the area under curve (AUC) of 0.86, and the AUC value for the combined all four isoforms was calculated to be 0.85. We have further verified [-2]proPSA, the dominant isoform, in an independent cohort of 34 clinical urine samples. Validation of proPSA isoforms in large-scale cohorts is needed to demonstrate their potential clinical utility.
Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Inmunoensayo , Isoformas de Proteínas , Espectrometría de MasasRESUMEN
Two studies (n = 1,522) examined the impact of role models in sport and science, technology, engineering, and mathematics (STEM) domains where gender discrimination has resulted in a lack of high-profile women. We examined the role of gender matching of personally known and famous exemplars on women's and men's motivation. Participants nominated a woman or man in sport (Study 1) or STEM (Study 2) who was either famous or known to them personally; they then indicated the extent to which they perceived this individual to be a motivating role model. Women and men were more motivated by personally known (vs. famous) role models. For famous exemplars, both women and men were most motivated by same-gender models (Studies 1 and 2). For personally known exemplars, men were similarly motivated by same- and other-gender models (Studies 1 and 2), but women were more motivated by same-gender models in sport (Study 1). Mediation analyses indicated that personally known (vs. famous) exemplars and, for women, same- (vs. other-) gender exemplars, were perceived as more attainable future selves and consequently were more motivating (Study 2). Given that there are fewer famous women in domains dominated by men, it is important to know if women can be inspired by personally known rather than famous individuals. These studies provide insight into the kinds of exemplars that are most motivating for women and may serve as a guide for educators and other practitioners seeking to provide the best role models for girls and women in domains dominated by men. Additional online materials for this article are available on PWQ's website athttp://journals.sagepub.com/doi/suppl/10.1177/03616843231156165.
RESUMEN
Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (ß = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (ß = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (qinteraction < 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids.