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Modulation of Notch signaling pathway in activated hepatic stellate cells does not ameliorate the outcome of liver fibrosis in carbon tetrachloride and DDC-feeding models.
Front Pharmacol
October 2024
Laboratory for Molecular Immunology, School of Medicine, Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia.
Background: Recent research suggests a possible role of Notch signaling pathway in development of liver fibrosis, but exact cellular and molecular mechanisms are still not well defined. Methods: We modulated Notch signaling in activated hepatic stellate cells/myofibroblasts using the model of inducible activation or inhibition of Notch signaling selective for αSMA positive cells in murine models of toxic fibrosis induced by CCl4 and cholestatic fibrosis induced by DDC supplemented feeding.
Results: Our results confirm that Notch signaling pathway is activated in both CCL4 and DDC model of liver fibrosis and that αSMA positive myofibroblasts are of activated hepatic stellate cells origin.
Phase 2 Trial of Regorafenib in Recurrent/Metastatic Adenoid Cystic Carcinoma.
Clin Cancer Res
December 2024
Head and Neck Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Article Synopsis
- - The study tested regorafenib, a multi-targeted tyrosine kinase inhibitor, for treating patients with recurrent/metastatic adenoid cystic carcinoma (ACC), aiming to evaluate its effectiveness and identify biomarkers related to treatment response.
- - Among 38 patients, no objective responses were observed, but 45% achieved 6-month progression-free survival (PFS), with longer PFS linked to specific immune-related tumor profiles and the presence of NOTCH1 or KDM6A alterations associated with poorer outcomes.
- - The findings suggest that combining CDK4/6 inhibitors with VEGFR-TKIs might improve treatment efficacy, emphasizing the need to consider the role of the immune microenvironment in ACC treatment resistance.
Abrogation of stemness in osteosarcoma by the mithramycin analog EC-8042 is mediated by its ability to inhibit NOTCH-1 signaling.
Biomed Pharmacother
June 2023
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n 33011, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias, 33011 Oviedo, Spain; CIBER en oncología (CIBERONC), 28029 Madrid, Spain. Electronic address:
Osteosarcomas are frequently associated to a poor prognosis and a modest response to current treatments. EC-8042 is a well-tolerated mithramycin analog that has demonstrated an efficient ability to eliminate tumor cells, including cancer stem cell subpopulations (CSC), in sarcomas. In transcriptomic and protein expression analyses, we identified NOTCH1 signaling as one of the main pro-stemness pathways repressed by EC-8042 in osteosarcomas.
View Article and Find Full Text PDFMethionine uptake via the SLC43A2 transporter is essential for regulatory T-cell survival.
Life Sci Alliance
September 2022
Institute for Stem Cell Science and Regenerative Medicine (DBT-inStem), Bengaluru, India
Cell death, survival, or growth decisions in T-cell subsets depend on interplay between cytokine-dependent and metabolic processes. The metabolic requirements of T-regulatory cells (Tregs) for their survival and how these are satisfied remain unclear. Herein, we identified a necessary requirement of methionine uptake and usage for Tregs survival upon IL-2 deprivation.
View Article and Find Full Text PDFInvolvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies.
Eur J Transl Myol
March 2022
King's College London, Randall Centre for Cell and Molecular Biophysics, Guy's Campus, London.
Neuromuscular disorders are a heterogeneous group of acquired or hereditary conditions that affect striated muscle function. The resulting decrease in muscle strength and motility irreversibly impacts quality of life. In addition to directly affecting skeletal muscle, pathogenesis can also arise from dysfunctional crosstalk between nerves and muscles, and may include cardiac impairment.
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