The cGAS-STING pathway has long been recognized as playing a crucial role in immune surveillance and tumor suppression. Here, we show that when the pathway is activated in a cancer-cell-autonomous response manner, it confers drug resistance. Targeted or conventional chemotherapy drugs promoted cytosolic DNA accumulation in cancer cells, activating the cGAS-STING pathway and downstream TBK1-IRF3/NF-κB signaling. This cancer cell-intrinsic response enabled the cells to counteract drug stress, allowing treatment resistance to be acquired and maintained. Blockade of stimulator of interferon genes (STING) signaling delayed and overcame resistance in models in vitro and in vivo. This finding uncovers an alternative face of cGAS-STING signaling other than the well-reported modulation of microenvironmental immune cells. It also implies a caution for the combination of STING agonist with targeted or conventional chemotherapy drug treatment, a strategy prevailing in current clinical trials.
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http://dx.doi.org/10.1016/j.chembiol.2023.05.005 | DOI Listing |
Vet Med Sci
January 2025
Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
A major risk to the poultry industry is antimicrobial resistance (AMR), specifically with regard to Mycoplasma gallisepticum (MG) infections. The sensitivity patterns of 100 MG isolates to biocides and antibiotics were examined in this study to clarify the interactions between antimicrobial agents and resistance mechanisms. The antimicrobial activity against MG was assessed using broth microdilution, and the results are shown as the minimum inhibitory concentration (MIC) for each strain, the MIC distribution (range), the MIC, and/or the MIC.
View Article and Find Full Text PDFCancer Med
January 2025
Faculty of Medical Sciences, Neuroscience Research Center, Lebanese University, Hadath, Lebanon.
Background: Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median survival of less than 15 months. Advancements in the field of epigenetics have expanded our understanding of cancer biology and helped explain the molecular heterogeneity of these tumors. B-cell-specific Moloney murine leukemia virus insertion site-1 (Bmi-1) is a member of the highly conserved polycomb group (PcG) protein family that acts as a transcriptional repressor of multiple genes, including those that determine cell proliferation and differentiation.
View Article and Find Full Text PDFJ Am Heart Assoc
January 2025
Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division Brigham and Women's Hospital and Harvard Medical School Boston MA USA.
Background: Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized.
Methods And Results: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) randomized 21 105 patients with atrial fibrillation and CHADS2 risk score ≥2 to higher-dose edoxaban regimen (60 mg daily, dose-reduced to 30 mg), lower-dose edoxaban regimen (30 mg, dose reduced to 15 mg, daily), or warfarin. Bleeds were adjudicated using International Society on Thrombosis and Haemostasis criteria.
Nat Commun
January 2025
Center for Integrative Genomics, University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland.
The energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Background: A rare reelin gene variant (RELN-COLBOS mutation) delayed dementia onset in almost 30 years in an autosomal dominant Alzheimer's disease (ADAD) carrier. This patient presented with high amyloid-β (Aβ) plaque load, but low tau accumulation, suggesting that this single-nucleotide polymorphism (SNP) in RELN conferred a resilience not only to cognitive decline but also to tauopathy in ADAD. However, whether RELN SNPs are also protective in sporadic Alzheimer's disease (AD) is yet to be determined.
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