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HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia.
J Clin Invest
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.
View Article and Find Full Text PDFElevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.
J Clin Invest
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.
View Article and Find Full Text PDFChitosan-Functionalized Fluorescent Calcium Carbonate Nanoparticle Loaded with Methotrexate: Future Theranostics for Triple Negative Breast Cancer.
ACS Biomater Sci Eng
January 2025
Nano 2 Micro Material Design Lab, Department of Chemical Engineering and Technology, IIT (BHU), Varanasi 221005, India.
Herein, fluorescent calcium carbonate nanoclusters encapsulated with methotrexate (Mtx) and surface functionalized with chitosan (25 nm) (@Calmat) have been developed for the imaging and treatment of triple-negative breast cancer (TNBC). These biocompatible, pH-sensitive nanoparticles demonstrate significant potential for targeted therapy and diagnostic applications. The efficacy of nanoparticles (NPs) was evaluated in MDA-MB-231 TNBC cell lines.
View Article and Find Full Text PDFTargeting oncogene-induced cellular plasticity for tumor therapy.
Adv Biotechnol (Singap)
July 2024
MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China.
Cellular plasticity, the remarkable adaptability of cancer cells to survive under various stress conditions, is a fundamental hallmark that significantly contributes to treatment resistance, tumor metastasis, and disease recurrence. Oncogenes, the driver genes that promote uncontrolled cell proliferation, have long been recognized as key drivers of cellular transformation and tumorigenesis. Paradoxically, accumulating evidence demonstrates that targeting certain oncogenes to inhibit tumor cell proliferation can unexpectedly induce processes like epithelial-to-mesenchymal transition (EMT), conferring enhanced invasive and metastatic capabilities.
View Article and Find Full Text PDFTargeted inhibition of PqsR in Pseudomonas aeruginosa PAO1 quorum-sensing network by chalcones as promising antibacterial compounds.
Mol Biol Rep
January 2025
Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Background: Pseudomonas aeruginosa's inherent and adapted resistance makes this pathogen a serious problem for antimicrobial treatments. Furthermore, its biofilm formation ability is the most critical armor against antimicrobial therapy, and the virulence factors, on the other hand, contribute to fatal infection and other recalcitrant phenotypic characteristics. These capabilities are harmonized through cell-cell communication called Quorum Sensing (QS), which results in gene expression regulation via three major interconnected circuits: las, rhl, and pqs system.
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