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The prevalence of brain tumors in males is common but unexplained. While sex differences in disease are typically mediated through acute sex hormone actions, sex-specific differences in brain tumor rates are comparable at all ages, suggesting that factors other than sex hormones underlie this discrepancy. We found that mesenchymal glioblastoma (Mes- GBM) affects more males as the result of cell-intrinsic sexual dimorphism in astrocyte transformation. We used astrocytes from neurofibromin-deficient ([Nf1.sup.-/-]) mice expressing a dominant-negative form of the tumor suppressor p53 (DNp53) and treated them with EGF as a Mes-GBM model. Male Mes-GBM astrocytes exhibited greater growth and colony formation compared with female Mes-GBM astrocytes. Moreover, male Mes-GBM astrocytes underwent greater tumorigenesis in vivo, regardless of recipient mouse sex. Male Mes-GBM astrocytes exhibited greater inactivation of the tumor suppressor RB, higher proliferation rates, and greater induction of a clonogenic, stem-like cell population compared with female Mes-GBM astrocytes. Furthermore, complete inactivation of RB and p53 in Mes-GBM astrocytes resulted in equivalent male and female tumorigenic transformation, indicating that intrinsic differences in RB activation are responsible for the predominance of tumorigenic transformation in male astrocytes. Together, these results indicate that cell-intrinsic sex differences in RB regulation and stem-like cell function may underlie the predominance of GBM in males., Introduction Throughout life, there are sex-specific differences in the prevalence of multiple human diseases. Many of these disparities, such as the rise in autoimmune diseases in women during their reproductive [...]

During the era of New Imperialism, the French state had the daunting task of convincing the French public of the need to support and to sustain an overseas empire. Stemming from its defeat in the Franco-Prussian War and hoping to regain its former global position, the French state set out to demonstrate the importance of maintaining an empire. Since the vast majority of the French people were apathetic towards colonial ventures, the French state used the 1889 Parisian Universal Exposition not only to educate the French about the economic benefits of the empire, but to entertain them simultaneously so that they would begin to accept the notion of an interconnected Greater France. This exposition contained a group of colonial exhibits in which indigenous colonial subjects, whom the expositions' organizers handpicked to come to France, showcased their daily lives and interacted with the visiting public. Visitors witnessed the daily routines of indigenous cultures and took away from the exhibits a greater understanding of those who lived in the colonies. However, the vast majority of the French public who visited the expositions did not experience a shift in their mindset and favored the continuance of a colonial empire. Until they could personally see an impact of the colonies onto their daily lives, the French public remained indifferent toward the French state's colonial ventures. [ABSTRACT FROM AUTHOR]

The prevalence of brain tumors in males is common but unexplained. While sex differences in disease are typically mediated through acute sex hormone actions, sex-specific differences in brain tumor rates are comparable at all ages, suggesting that factors other than sex hormones underlie this discrepancy. We found that mesenchymal glioblastoma (Mes-GBM) affects more males as the result of cell-intrinsic sexual dimorphism in astrocyte transformation. We used astrocytes from neurofibromin-deficient (Nf1-/-) mice expressing a dominant-negative form of the tumor suppressor p53 (DNp53) and treated them with EGF as a Mes-GBM model. Male Mes-GBM astrocytes exhibited greater growth and colony formation compared with female Mes-GBM astrocytes. Moreover, male Mes-GBM astrocytes underwent greater tumorigenesis in vivo, regardless of recipient mouse sex. Male Mes-GBM astrocytes exhibited greater inactivation of the tumor suppressor RB, higher proliferation rates, and greater induction of a clonogenic, stem-like cell population compared with female Mes-GBM astrocytes. Furthermore, complete inactivation of RB and p53 in Mes-GBM astrocytes resulted in equivalent male and female tumorigenic transformation, indicating that intrinsic differences in RB activation are responsible for the predominance of tumorigenic transformation in male astrocytes. Together, these results indicate that cell-intrinsic sex differences in RB regulation and stem-like cell function may underlie the predominance of GBM in males. [ABSTRACT FROM AUTHOR]

Estrogen-receptor-positive breast tumors are treated with anti-estrogen (AE) therapies but frequently develop resistance. Cancer stem cells (CSCs) with high aldehyde dehydrogenase activity (ALDH + cells) are enriched following AE treatment. Here, we show that the interleukin-1β (IL-1β) signaling pathway is activated in ALDH + cells, and data from single cells reveals that AE treatment selects for IL-1 receptor (IL1R1)-expressing ALDH + cells. Importantly, CSC activity is reduced by an IL1R1 inhibitor in AE-resistant models. Moreover, IL1R1 expression is increased in the tumors of patients treated with AE therapy and predicts treatment failure. Single-cell gene expression analysis revealed that at least two subpopulations exist within the ALDH + population, one proliferative and one quiescent. Following AE therapy the quiescent population is expanded, which suggests CSC dormancy as an adaptive strategy that facilitates treatment resistance. Targeting of ALDH + IL1R1 + cells merits testing as a strategy to combat AE resistance in patients with residual disease., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)