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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 PDFAllogeneic DNT cell therapy synergizes with T cells to promote anti-leukemic activities while suppressing GvHD.
J Exp Clin Cancer Res
January 2025
Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a second-line treatment with curative potential for leukemia patients. However, the prognosis of allo-HSCT patients with disease relapse or graft-versus-host disease (GvHD) is poor. CD4 or CD8 conventional T (Tconv) cells are critically involved in mediating anti-leukemic immune responses to prevent relapse and detrimental GvHD.
View Article and Find Full Text PDFSynthesis, biological activities, DFT calculations and molecular docking studies of O-methyl-inositols.
Chem Biodivers
January 2025
Ordu University: Ordu Universitesi, Department of Chemistry, Cumhuriyet Mah., Ordu, TURKEY.
The concise synthesis of O-methyled-inositol derivative and conduritol derivatives was obtained starting from p-benzoquinone. Spectroscopic methods have been performed for characterization of new synthesized compounds. Cyclitols are useful molecules with anticancer, antibiotic, antinutrient and antileukemic activity.
View Article and Find Full Text PDFImpact of corticosteroids on the efficacy of CD19/22 CAR-T cell therapy in pediatric patients with B-ALL: a single-center study.
Front Pediatr
January 2025
Department of Cell Immunotherapy, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Introduction: Corticosteroids are used for toxicity management, raising concerns about whether they may affect the anti-leukemic effects of chimeric antigen receptor (CAR)-T cells.
Methods And Results: In this study, we retrospectively analyzed patients (fined two subgroups based on disease burden. Of the 75 cases in the low disease burden (LDB) group (MRD < 5%, no extramedullary disease), there was no significant difference between the use of steroids and event-free survival (EFS) ( = 0.
Synthesis, characterization, and computational evaluation of some synthesized xanthone derivatives: focus on kinase target network and biomedical properties.
Front Pharmacol
January 2025
Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
Background: Xanthones are dubbed as putative lead-like molecules for cancer drug design and discovery. This study was aimed at the synthesis, characterization, and target fishing of novel xanthone derivatives.
Methods: The products of reactions of xanthydrol with urea, thiourea, and thiosemicarbazide reacted with α-haloketones to prepare the thiazolone compounds.
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