In this review, we compare and contrast the most frequent mechanisms of antiandrogen and antiestrogen resistance, and provide potential therapeutic strategies for targeting both advanced PCa and BCa.Brown adipose tissue (BAT) is a metabolically active organ that exhibits sex-differential features, that is, being generally more abundant and active in females than in males. Although sex steroids, particularly estrogens, have been shown to regulate BAT thermogenic function, the underlying molecular mechanisms contributing to sexual dimorphism in basal BAT activity have not been elucidated. Therefore, we assessed the transcriptome of interscapular BAT of male and female C57BL/6J mice by RNA sequencing and identified 295 genes showing ≥2-fold differential expression (adjusted P less then 0.05). In silico functional annotation clustering suggested an enrichment of genes encoding proteins involved in cell-cell contact, interaction, and adhesion. Ovariectomy reduced the expression of these genes in female BAT toward a male pattern whereas orchiectomy had marginal effects on the transcriptional pattern, indicating a prominent role of female gonadal hormones in this sex-differential expression pattern. Progesterone was identified as a possible upstream regulator of the sex-differentially expressed genes. Studying the direct effects of progesterone in vitro in primary adipocytes showed that progesterone significantly altered the transcription of several of the identified genes, possibly via the glucocorticoid receptor. In conclusion, this study reveals a sexually dimorphic transcription profile in murine BAT at general housing conditions and demonstrates a role for progesterone in the regulation of the interscapular BAT transcriptome.Endothelial dysfunction is a prominent feature of preeclampsia, a hypertensive disorder of pregnancy, and contributes to multiple symptoms characteristic of the syndrome. A myriad of growth factors and cytokines are dysregulated in preeclampsia as compared to normal pregnancy, however, a complete appreciation of the effect of changing concentrations of these factors on endothelial function is lacking. In this study, we evaluate the effect of a variety of growth factors and cytokines on Ca2+ signaling and monolayer integrity. We report that VEGF165, TNFα, EGF, and IL-1β either improve or inhibit Ca2+ signaling depending on dose, whereas TNFα and IL-1β reduce monolayer integrity and bFGF increases monolayer integrity. Additionally, to model the effects of combinations of growth factors and cytokines, we screened for Ca2+ signaling changes in response to 16 dose combinations of VEGF165 and TNFα together. This revealed an optimal combination capable of supporting pregnancy-adapted Ca2+ signaling, and that changes in either VEGF165 or TNFα dose would result in a shift toward suppressed function. This study shows in detail how growth factor or cytokine concentration effects endothelial cell function. Such data can be used to model how changing growth factor and cytokine levels in normal pregnancy may contribute to healthy endothelial function and in preeclampsia may promote endothelial dysfunction. The results of VEGF165 and TNFα combination treatments suggest that more complex growth factor and cytokine combination modeling may be important in order to more accurately understand the effects of circulating factors on the endothelial function.Acylated ghrelin (AG) is a gut-derived peptide with growth hormone secretagogue (GHS), orexigenic and other physiological activities mediated by GHS receptor-1a (GHSR). Ghrelin occurs in unacylated form (UAG) with activities opposing AG, although its mechanism of action is unknown. UAG does not antagonize AG at GHSR, and has biological effects on cells that lack this receptor. Because UAG binds to cells, it has been hypothesized that UAG acts via a cell-surface receptor, although this has not been confirmed. This study aimed to identify cell surface proteins to which UAG binds that could modulate or mediate its biological effects. The MCF7 cell-line was used as a model because UAG induces ERK signaling in these cells in the absence of GHSR. Using ligand-receptor capture and LC-MS/MS we identified specific heparan-sulfate proteoglycans (HSPGs) to which UAG interacts on cell surfaces. In line with this, UAG, as well as AG, bind with high affinity to heparin, and heparin and heparinase treatment suppress, whereas HSPG overexpression increases, UAG binding to MCF7 cell surfaces. Moreover, heparin suppresses the ERK response to UAG. However, conversion of the lysines in UAG to alanine, which prevents its binding to heparin and cell surface HSPGs, does not prevent its activation of ERK. Our data show that the interaction of UAG with HSPGs modulates its biological activity in cells. More broadly, the interaction of UAG and AG with HSPGs could be important for the specificity and potency of their biological action in vivo. Companies use brand websites as a promotional tool to engage consumers on the web, which can increase product use. Given that some products are harmful to the health of consumers, it is important for marketing associated with these products to be subject to public health surveillance. However, terms of service (TOS) governing the use of brand website content may impede such important research. The aim of this study is to explore the TOS for brand websites with public health significance to assess possible legal and ethical challenges for conducting research on consumer product websites. Using Statista, we purposefully constructed a sample of 15 leading American tobacco, alcohol, psychiatric pharmaceutical, fast-food, and gun brands that have associated websites. We developed and implemented a structured coding system for the TOS on these websites and coded for the presence versus absence of different types of restriction that might impact the ability to conduct research. All TOS stated that by accessiy having the user's Internet Protocol address blocked, terminating log-in credentials, or enforcing legal action resulting in civil or criminal penalties. TOS create complications for public health surveillance related to e-marketing on brand websites. CC-92480 modulator Recent court opinions have reduced the risk of federal criminal charges for violating TOS on public websites, but this risk remains unclear for private websites. The public health community needs to establish standards to guide and protect researchers from the possibility of legal repercussions related to such efforts.TOS create complications for public health surveillance related to e-marketing on brand websites. Recent court opinions have reduced the risk of federal criminal charges for violating TOS on public websites, but this risk remains unclear for private websites. The public health community needs to establish standards to guide and protect researchers from the possibility of legal repercussions related to such efforts.