Histological grading of 126 oestrogen receptor positive and 81 oestrogen receptor negative breast carcinomas, using the WHO system, showed that some tumours in all grades had high receptor values, others low. There was no correlation between the receptor values and histological grade. It is suggested that factors other than the degree of dedifferentiation of the tumour may be responsible for the consistent tendency for receptor negative tumours to be placed in a high histological grade.
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http://dx.doi.org/10.1111/j.1365-2559.1981.tb01784.x | DOI Listing |
Nature
January 2025
Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, USA.
Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.
View Article and Find Full Text PDFPharm Res
January 2025
Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, 17033, USA.
Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, C 1x), decursinol angelate (DA, C ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, C ~ 1000x).
View Article and Find Full Text PDFNature
January 2025
Case Comprehensive Cancer Center and Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
The oestrogen receptor (ER or ERα), a nuclear hormone receptor that drives most breast cancer, is commonly activated by phosphorylation at serine 118 within its intrinsically disordered N-terminal transactivation domain. Although this modification enables oestrogen-independent ER function, its mechanism has remained unclear despite ongoing clinical trials of kinase inhibitors targeting this region. By integration of small-angle X-ray scattering and nuclear magnetic resonance spectroscopy with functional studies, we show that serine 118 phosphorylation triggers an unexpected expansion of the disordered domain and disrupts specific hydrophobic clustering between two aromatic-rich regions.
View Article and Find Full Text PDFExp Neurol
January 2025
Department of Neurology, University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; UVA Brain Institute, University of Virginia, Charlottesville, VA 22908, USA.
Migraine patients often experience sensory symptoms called auras accompanying the headaches. Cortical spreading depression (CSD), a slow-propagating wave of neuroglial depolarization followed by hyperpolarization is proposed to be the neurological mechanism underlying these auras. We have previously found that progesterone regulates susceptibility to migraine through progesterone receptor (PR) activation.
View Article and Find Full Text PDFAnim Reprod
December 2024
Department of Animal Science, South Dakota State University, Brookings, SD, U.S.A.
Early puberty is associated with improved long-term reproductive performance. Predicting who will achieve early puberty is limited to intensive, invasive serial blood collections for measurement of reproductive hormones. The vaginal genome during pubertal development has potential as biomarkers of early estrus in the pre-pubertal period.
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