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Why are we still in need for novel anti-obesity medications?
Lancet Reg Health Eur
December 2024
Institute for Diabetes and Obesity, Helmholtz Munich, Neuherberg, Germany.
From the pioneering moment in 1987 when the insulinotropic effect of glucagon-like peptide 1 (GLP-1) was first demonstrated in humans, to today's pharmaceutical gold rush for GLP-1-based treatments of obesity, the journey of GLP-1 pharmacology has been nothing short of extraordinary. The sequential conceptual developments of long-acting GLP-1 receptor (GLP-1R) mono-agonists, GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonists, and GLP-1R/GIPR/glucagon receptor (GcgR) triple agonists, have led to profound body weight-lowering capacities, with benefits that extend past obesity and towards obesity-associated diseases. The GLP-1R/GIPR dual-agonist tirzepatide has demonstrated a remarkable 23% body weight reduction in individuals with obesity over 72 weeks, eclipsing the average result achieved by certain types of bariatric surgery.
View Article and Find Full Text PDFA Collection of Novel Antitumor Agents That Regulate Lipid Metabolism in the Tumor Microenvironment.
J Med Chem
December 2024
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China.
Lipid metabolism disorder is the cause of one of the most significant metabolic changes in tumors. In the process of tumor occurrence and development, tumor cells choose a continuous metabolic adaptation to accommodate the changing environment to the maximum extent possible. In a variety of tumors, the uptake, production, and storage of lipids are generally upregulated.
View Article and Find Full Text PDFProtein kinase CK2 sustains de novo fatty acid synthesis by regulating the expression of SCD-1 in human renal cancer cells.
Cancer Cell Int
December 2024
Department of Biochemistry, Western University, London, ON, Canada.
Background: Clear cell renal cell carcinoma (ccRCC) is a type of cancer characterized by a vast intracellular accumulation of lipids that are critical to sustain growth and viability of the cells in the tumour microenvironment. Stearoyl-CoA 9-desaturase 1 (SCD-1) is an essential enzyme for the synthesis of monounsaturated fatty acids and consistently overexpressed in all stages of ccRCC growth.
Methods: Human clear cell renal cell carcinoma lines were treated with small-molecule inhibitors of protein kinase CK2.
Comparison of Alcohol Septal Ablation with Mavacamten in Obstructive Hypertrophic Cardiomyopathy.
Am J Cardiol
December 2024
Northwestern University, Feinberg School of Medicine, Chicago IL 60611; The Hypertrophic Cardiomyopathy Program at the Bluhm Cardiovascular Institute, Chicago IL 60611; Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago IL 60611.
Background: Obstructive hypertrophic cardiomyopathy (HCM) is associated with significant morbidity due to left ventricular outflow tract (LVOT) obstruction. While alcohol septal ablation (ASA) is an established interventional treatment, mavacamten, a novel cardiac myosin inhibitor, has emerged as a non-invasive pharmacological alternative. Understanding the comparative efficacy of these two treatments is important for optimizing patient care.
View Article and Find Full Text PDFWEE1 Confers Resistance to KRAS Inhibitors in Non-Small Cell Lung Cancer.
Cancer Lett
December 2024
Division of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan; Division of Translational Genomics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan. Electronic address:
KRAS inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS inhibitors must be developed.
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