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http://dx.doi.org/10.1200/PO.23.00217 | DOI Listing |
Nat Cancer
January 2025
Department of Oncological Sciences, Precision Immunology Institute, the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Cyclin-dependent kinases (CDKs) 4 and 6 (CDK4/6) are important regulators of the cell cycle. Selective CDK4/6 small-molecule inhibitors have shown clinical activity in hormonal receptor-positive (HR) metastatic breast cancer, but their effectiveness remains limited in other cancer types. CDK4/6 degradation and improved selectivity across CDK paralogs are approaches that could expand the effectiveness of CDK4/6 targeting.
View Article and Find Full Text PDFActa 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 PDFLeukemia
January 2025
Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
Multiple myeloma (MM) remains an incurable hematological malignancy that necessitates the identification of novel therapeutic strategies. Here, we report that intracellular levels of very long chain fatty acids (VLCFAs) control the cytotoxicity of MM chemotherapeutic agents. Inhibition of VLCFA biosynthesis reduced cell death in MM cells caused by the proteasome inhibitor, bortezomib.
View Article and Find Full Text PDFMol Neurobiol
January 2025
Research and Innovation Center, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China.
Investigating plasma proteomic signatures of dementia offers insights into its pathology, aids biomarker discovery, supports disease monitoring, and informs drug development. Here, we analyzed data from 48,367 UK Biobank participants with proteomic profiling. Using Cox and generalized linear models, we examined the longitudinal associations between proteomic signatures and dementia-related phenotypes.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Cardiovascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address:
The functional food application of edible fungus polysaccharides has been widely studied based on their variety of potential pharmacological activities. However, the hepatoprotective effects and mechanisms of Morchella esculenta polysaccharide against nonalcoholic fatty liver disease (NAFLD) remain unknown. A high-fat diet (HFD) fed C57BL/6 J mice for 8 weeks was employed to establish NAFLD with simple steatosis, methionine choline deficiency (MCD) diet for 4 weeks induced hepatic steatohepatitis and fibrosis.
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