Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human cancers and is associated with extensive desmoplastic changes in the tumor microenvironment. In this issue of , two studies by Cortes 1, 2 identify the G‐protein‐coupled estrogen receptor (GPER) as an important regulator of the PDAC‐associated stroma, modulating tissue stiffness, hypoxic responses, and desmoplasia. Intriguingly, the authors find that tamoxifen, which is widely used for its antagonizing effect on nuclear estrogen receptor (ER)‐positive breast cancers, acts as GPER agonist to normalize the PDAC microenvironment. The two studies thus open up new opportunities to explore tamoxifen as potential anti‐stromal therapy in PDAC.
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http://dx.doi.org/10.15252/embr.201847334 | DOI Listing |
J Biochem
January 2025
Department of Comparative and Experimental Medicine, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
The uterine endometrium consists of luminal epithelium, glandular epithelium, and stromal cells, with uterine glands playing a pivotal role in pregnancy success among mammals. Uterine glands secrete essential factors that regulate embryo development and implantation; however, their cellular biology remains poorly understood. This study presents a refined method for isolating three distinct endometrial cell types with high purity, with a specific emphasis on glandular epithelial cells.
View Article and Find Full Text PDFAging Adv
December 2024
Department of Integrative Genomics and Epidemiology, Meharry Medical College, Nashville, TN, USA.
Estrogen hormones are primarily associated with their role as female sex hormones responsible for primary and secondary sexual development. Estrogen receptors are known to undergo age-dependent decreases due to age-related changes in hormone production. In the mitochondria, estrogen functions by reducing the production of reactive oxygen species in the electron transport chain, inhibiting apoptosis, and regulating mitochondrial DNA content.
View Article and Find Full Text PDFEnviron Health (Wash)
January 2025
Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02543, United States.
In May 2021, the M/V ship fire disaster led to the largest maritime spill of resin pellets (nurdles) and burnt plastic (pyroplastic). Field samples collected from beaches in Sri Lanka nearest to the ship comprised nurdles and pieces of pyroplastic. Three years later, the toxicity of the spilled material remains unresolved.
View Article and Find Full Text PDFPatients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.
View Article and Find Full Text PDFNat Med
January 2025
University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.
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