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Development of an F-labeled 5-aroylindole derivative for histone deacetylase 6 imaging in spinocerebellar ataxia.
Appl Radiat Isot
December 2024
Department of Isotope Application Research, National Atomic Research Institute, Taoyuan City, Taiwan, ROC.
Histone deacetylase 6 (HDAC6) is an enzyme crucial in epigenetic regulation and protein degradation, with implications in various cancers and neurodegenerative disorders. While HDAC6 is recognized as a promising therapeutic target for Parkinson's and Alzheimer's diseases, its involvement in spinocerebellar ataxias (SCAs) remains underexplored. Currently, there are no direct methods available for characterizing HDAC6 in the brains of living subjects.
View Article and Find Full Text PDFEpidermal Growth Factor Receptors Unveiled: A Comprehensive Survey on Mutations, Clinical Insights of Global Inhibitors, and Emergence of Heterocyclic Derivatives as EGFR Inhibitors.
J Drug Target
January 2025
Department of Pharmacology, Orotta College of Medicine and Health Sciences, Asmara University, Asmara, P.O. Box: 10549, Eritrea; (I.P).
Mutations that overexpress the epidermal growth factor receptor (EGFR) are linked to cancers like breast (15-20%), head and neck (10-15%), colorectal (5-8%), and non-small cell lung cancer (10-50%), especially in East Asian populations. EGFR activation stimulates "RAS/RAF/MEK/ERK, PI3K/Akt, and MAPK" pathways, which enhance cell division, survival, angiogenesis, and tumor growth while inhibiting apoptosis and metastasis. Secondary mutations (e.
View Article and Find Full Text PDFSLC7A5 is required for cancer cell growth under arginine-limited conditions.
Cell Rep
January 2025
Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:
Tumor cells must optimize metabolite acquisition between synthesis and uptake from a microenvironment characterized by hypoxia, lactate accumulation, and depletion of many amino acids, including arginine. We performed a metabolism-focused functional screen using CRISPR-Cas9 to identify pathways and factors that enable tumor growth in an arginine-depleted environment. Our screen identified the SLC-family transporter SLC7A5 as required for growth, and we hypothesized that this protein functions as a high-affinity citrulline transporter.
View Article and Find Full Text PDFRef-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.
Angiogenesis
January 2025
Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).
View Article and Find Full Text PDFBiologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.
HGG Adv
January 2025
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).
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