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Platelets as crucial players in the dynamic interplay of inflammation, immunity, and cancer: unveiling new strategies for cancer prevention.
Front Pharmacol
December 2024
Systems Pharmacology and Translational Therapeutics Laboratory, The Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University, Chieti, Italy.
Inflammation plays a critical role in the pathogenesis of various diseases by promoting the acquisition of new functional traits by different cell types. Shared risk factors between cardiovascular disease and cancer, including smoking, obesity, diabetes, high-fat diet, low physical activity, and alcohol consumption, contribute to inflammation linked to platelet activation. Platelets contribute to an inflammatory state by activating various normal cells, such as fibroblasts, immune cells, and vascular cells.
View Article and Find Full Text PDFMany agents that show promise in preclinical cancer models lack efficacy in patients due to patient heterogeneity that is not captured in traditional assays. To address this problem, we have developed GENEVA, a platform that measures the molecular and phenotypic consequences of drug perturbations within diverse populations of cancer cells at single-cell resolution, both and . Here, we apply GENEVA to study the KRAS G12C inhibitors, recapitulating known properties of these drugs and uncovering a previously unknown role for mitochondrial activation in cell death induced by KRAS inhibition.
View Article and Find Full Text PDFUnraveling Caco-2 Cells through Functional and Transcriptomic Assessments.
Regul Toxicol Pharmacol
January 2025
Division of Applied Regulatory Science, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, The U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, United States of America. Electronic address:
The static Caco-2 monolayer is an extensively utilized model for predicting the permeability of small molecules during the drug development process. While these cells can differentiate and develop key functional and morphological features that emulate human enterocytes, they do not fully replicate the complexity of human intestinal physiology. In this study, we investigated functional and morphological aspects of Caco-2 cells, alongside their transcriptomic profiles, with a particular emphasis on genes encoding drug-metabolizing enzymes and drug transporters.
View Article and Find Full Text PDFHsa_circ_0002005 aggravates osteosarcoma by increasing cell proliferation, migration, and invasion.
Gene
January 2025
Department of Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, No. 166 East University Road, Nanning 530005, Guangxi, PR China. Electronic address:
Emerging evidence suggests that circular RNAs (circRNAs), a class of non-coding RNAs, play a critical role in the progression of several cancers, including osteosarcoma (OS). In this study, we focused on a specific circRNA, hsa_circ_0002005, derived from the mesoderm-induced early response 1 family member 2 (MIER2) gene. We determined the expression levels of hsa_circ_0002005 in OS samples through the use of real-time quantitative polymerase chain reaction (RT-qPCR).
View Article and Find Full Text PDFPegylated solid lipid nanoparticles for the intranasal delivery of combination antiretroviral therapy composed of Atazanavir and Elvitegravir to treat NeuroAIDS.
Int J Pharm
January 2025
College of Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284, USA. Electronic address:
Intranasal drug administration offers a promising strategy for delivering combination antiretroviral therapy (cART) directly to the central nervous system to treat NeuroAIDS, leveraging the nose-to-brain route to bypass the blood-brain barrier. However, challenges such as enzymatic degradation in the nasal mucosa, low permeability, and mucociliary clearance within the nasal cavity must first be addressed to make this route feasible. To overcome these barriers, this study developed solid lipid nanoparticles (SLNs) with varying PEGylation levels (0 %, 5 %, 10 %, and 15 % w/w of PEGylated lipid), co-encapsulated with Elvitegravir (EVG) and Atazanavir (ATZ) as an integrase and protease inhibitor, respectively.
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