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Probing the physical hallmarks of cancer.
Nat Methods
January 2025
Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
The physical microenvironment plays a crucial role in tumor development, progression, metastasis and treatment. Recently, we proposed four physical hallmarks of cancer, with distinct origins and consequences, to characterize abnormalities in the physical tumor microenvironment: (1) elevated compressive-tensile solid stresses, (2) elevated interstitial fluid pressure and the resulting interstitial fluid flow, (3) altered material properties (for example, increased tissue stiffness) and (4) altered physical micro-architecture. As this emerging field of physical oncology is being advanced by tumor biologists, cell and developmental biologists, engineers, physicists and oncologists, there is a critical need for model systems and measurement tools to mechanistically probe these physical hallmarks.
View Article and Find Full Text PDFProlactin-induced sensitization of trigeminal nociceptors promotes migraine co-morbidity in endometriosis.
Cephalalgia
January 2025
Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA.
Background: Women with endometriosis are more likely to have migraine. The mechanisms underlying this co-morbidity are unknown. Prolactin, a neurohormone secreted and released into circulation from the anterior pituitary, can sensitize sensory neurons from female, but not male, rodents, monkeys and human donors.
View Article and Find Full Text PDFSynaptic Targets and Cellular Sources of CB1 Cannabinoid Receptor and Vesicular Glutamate Transporter-3 Expressing Nerve Terminals in Relation to GABAergic Neurons in the Human Cerebral Cortex.
Eur J Neurosci
January 2025
Department of Pharmacology, University of Oxford, Oxford, UK.
Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunoreactive axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3.
View Article and Find Full Text PDFCo-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden.
NPJ Breast Cancer
January 2025
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet.
View Article and Find Full Text PDFA novel semi-quantitative scoring method for CD8+ tumor-infiltrating lymphocytes based on infiltration sites in gastric cancer.
Am J Cancer Res
December 2024
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
No established method currently exists for evaluating tumor-infiltrating lymphocytes (TILs) in gastric cancer (GC), and their clinical significance based on infiltration site in GC remains unclear. In this study, we developed a method to evaluate TILs according to their infiltration site as a prognostic marker for GC. We retrospectively analyzed 103 patients with advanced GC who underwent curative resection.
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