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Concurrent inhibition of p300/CBP and FLT3 enhances cytotoxicity and overcomes resistance in acute myeloid leukemia.
Acta Pharmacol Sin
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
FMS-like tyrosine kinase-3 (FLT3), a class 3 receptor tyrosine kinase, can be activated by mutations of internal tandem duplication (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD), leading to constitutive activation of downstream signaling cascades, including the JAK/STAT5, PI3K/AKT/mTOR and RAS/MAPK pathways, which promote the progression of leukemic cells. Despite the initial promise of FLT3 inhibitors, the discouraging outcomes in the treatment of FLT3-ITD-positive acute myeloid leukemia (AML) promote the pursuit of more potent and enduring therapeutic approaches. The histone acetyltransferase complex comprising the E1A binding protein P300 and its paralog CREB-binding protein (p300/CBP) is a promising therapeutic target, but the development of effective p300/CBP inhibitors faces challenges due to inherent resistance and low efficacy, often exacerbated by the absence of reliable clinical biomarkers for patient stratification.
View Article and Find Full Text PDFA comparative analysis of collagen based dressings and polysaccharide microspheres for hemostasis management in hepatic stab wounds.
Sci Rep
January 2025
General and Digestive Unit, Central Hospital of Defense, Spanish-Ministry of Defense, Glorieta del Ejército, 1, 28047, Madrid, Spain.
This study aims to evaluate two of the most commonly used products, the collagen-based patch (Hemopatch) and the micropolysaccharide microspheres powder (Perclot), in the context of stab liver injury in pigs. The objectives of this study were to assess blood loss at various time intervals up to 24 h, survival rates, and mean arterial pressure. The research involved 18 Large-White swine.
View Article and Find Full Text PDFUtilization of a human Liver Tissue Chip for drug-metabolizing enzyme induction studies of perpetrator and victim drugs.
Drug Metab Dispos
January 2025
Javelin Biotech, Inc, Woburn, Massachusetts. Electronic address:
Polypharmacy-related drug-drug interactions (DDIs) are a significant and growing healthcare concern. An increasing number of therapeutic drugs on the market underscores the necessity to accurately assess new drug combinations during preclinical evaluation for DDIs. In vitro primary human hepatocytes (PHH) models are only applicable for short-term induction studies because of their rapid loss of metabolic function.
View Article and Find Full Text PDFForecasting Asparaginase Need and Cost for Childhood Cancer Using ACCESS FORxECAST.
JCO Glob Oncol
January 2025
Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada.
Purpose: Asparaginase (ASN) is a critical component of pediatric ALL protocols. Until recently, ASN was available in three formulations: native Escherichia coli, PEGylated E. coli (PEG), and Erwinase, with native E.
View Article and Find Full Text PDFArtificial Intelligence in Retrosynthesis Prediction and its Applications in Medicinal Chemistry.
J Med Chem
January 2025
Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Retrosynthesis is a strategy to analyze the synthetic routes for target molecules in medicinal chemistry. However, traditional retrosynthesis predictions performed by chemists and rule-based expert systems struggle to adapt to the vast chemical space of real-world scenarios. Artificial intelligence (AI) has revolutionized retrosynthesis prediction in recent decades, significantly increasing the accuracy and diversity of predictions for target compounds.
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