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The transforming growth factor β (TGF-β) pathway, which is well studied for its ability to inhibit cell proliferation in early stages of tumorigenesis while promoting epithelial-mesenchymal transition and invasion in advanced cancer, is considered to act as a double-edged sword in cancer. Multiple inhibitors have been developed to target TGF-β signaling, but results from clinical trials were inconsistent, suggesting that the functions of TGF-β in human cancers are not yet fully explored. Multiple drug resistance is a major challenge in cancer therapy; emerging evidence indicates that TGF-β signaling may be a key factor in cancer resistance to chemotherapy, targeted therapy and immunotherapy. Finally, combining anti-TGF-β therapy with other cancer therapy is an attractive venue to be explored for the treatment of therapy-resistant cancer.
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http://dx.doi.org/10.3389/fcell.2021.786728 | DOI Listing |
Acta Neuropathol Commun
September 2025
Department of Biomedical and Clinical Sciences and Department of Clinical Pathology, Linköping University, 58185, Linköping, Sweden.
Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD.
View Article and Find Full Text PDFJ Biomed Sci
September 2025
Division of Gastroenterology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Oncometabolites are aberrant metabolic byproducts that arise from mutations in enzymes of the tricarboxylic acid (TCA) cycle or related metabolic pathways and play central roles in tumor progression and immune evasion. Among these, 2-hydroxyglutarate (2-HG), succinate, and fumarate are the most well-characterized, acting as competitive inhibitors of α-ketoglutarate-dependent dioxygenases to alter DNA and histone methylation, cellular differentiation, and hypoxia signaling. More recently, itaconate, an immunometabolite predominantly produced by activated macrophages, has been recognized for its dual roles in modulating inflammation and tumor immunity.
View Article and Find Full Text PDFCell Commun Signal
September 2025
Department of Cytology, Institute of Anatomy, Medical Faculty, Ruhr-University Bochum, Universitätsstr. 150, Building MA 5/52, Bochum, 44801, Germany.
Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by oxidative stress and progressive motor neuron degeneration. This study evaluates the potential neuroprotective effects of caffeine in the Wobbler mouse, an established model of ALS.
Methods: Wobbler mice received caffeine supplementation (60 mg/kg/day) via drinking water, and key parameters, including muscle strength, NAD metabolism, oxidative stress, and motor neuron morphology, were assessed at critical disease stages.
Fundam Clin Pharmacol
October 2025
Postgraduate Program in Pharmaceutical Science, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil.
This review highlights the integration of drug repurposing and nanotechnology-driven delivery strategies as innovative approaches to enhance the antifungal activity of statins against mucosal candidiasis, providing a framework for future translational research and clinical application. The rising prevalence of antifungal resistance and virulence factors of Candida albicans underscore the limitations of current therapies. Statins, commonly used as lipid-lowering agents, have emerged as attractive repurposed drug candidates due to their ability to interfere with fungal ergosterol biosynthesis and Ras-mediated signaling pathways.
View Article and Find Full Text PDFStem Cell Rev Rep
September 2025
Paris Cité University, INSERM UMR-S 970, Paris Cardiovascular Research Centre, Paris, France.
Endothelial Colony-Forming Cells (ECFCs) are recognized as key vasculogenic progenitors in humans and serve as valuable liquid biopsies for diagnosing and studying vascular disorders. In a groundbreaking study, Anceschi et al. present a novel, integrative strategy that combines ECFCs loaded with gold nanorods (AuNRs) to enhance tumor radiosensitization through localized hyperthermia.
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