Role of Membrane Estrogen Receptor Alpha on the Positive Feedback of Estrogens on Kisspeptin and GnRH Neurons.

Estrogens act through nuclear and membrane-initiated signaling. Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contribution of its nuclear and membrane signaling to the central regulation of reproduction is unclear. To address this question, two complementary approaches were used: estetrol (E) a natural estrogen acting as an agonist of nuclear ERs, but as an antagonist of their membrane fraction, and the C451A-ERα mouse lacking mERα.

Real-world evaluation of access-driven Canadian treatment sequences in progressive prostate cancer (REACTIVATE).

Introduction: The results of the phase 3 ALSYMPCA trial showed that Radium-223 (Ra-223) improves overall survival (OS) and delays onset of first symptomatic skeletal event vs. placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the REACTIVATE study was to inform the optimal placement of Ra-233 in the treatment sequence by evaluating clinical outcomes and healthcare resource utilization using real-world data from multiple Canadian provinces.

Safety of immune checkpoint inhibitor rechallenge after severe immune-related adverse events: a retrospective analysis.

Immune checkpoint inhibitors (ICIs) present clinicians with the challenge of managing immune-related adverse events (irAEs), which can range from mild to severe due to immune system activation . While guidelines recommend discontinuing ICIs for grade 3 partial and all grade 4 irAEs, there is growing interest in rechallenging patients based on oncological outcomes, particularly for cardiovascular and neurological irAEs where data remains scarce . We retrospectively evaluated the safety of ICI rechallenge following grade 3-4 irAEs, specifically focusing on cardiovascular and neurological events, in patients discussed at our multidisciplinary immunotoxicity assessment board between 2019 and 2021.