Cell-cycle dysregulation is a hallmark of tumor cells. The ability of normal cells to undergo cell-cycle arrest after damage to DNA is crucial for the maintenance of genomic integrity. The biochemical pathways that stop the cell cycle in response to cellular stressors are called checkpoints. Defective checkpoint function results in genetic modifications that contribute to tumorigenesis. The regulation of checkpoint signaling also has important clinical implications because the abrogation of checkpoint function can alter the sensitivity of tumor cells to chemotherapeutics. Here, we provide an overview of the mechanisms that regulate the cell cycle, current anticancer therapies that target checkpoint signaling pathways, and strategies for the development of novel chemotherapeutic agents.
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http://dx.doi.org/10.1016/S0165-6147(03)00026-9 | DOI Listing |
Elife
January 2025
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Vanderbilt University Medical Center, Nashville, TN, USA.
Background: Manganese (Mn) is an essential metal that serves as a cofactor for metalloenzymes important in moderating the glutamate/glutamine cycle and other oxidative stress pathways. Typically, Mn is acquired through the diet, however, Mn overexposure can arise through drinking inadequately treated well water or inhalation of Mn-containing industrial byproducts. Mn toxicity disrupts dopaminergic neurotransmission resulting in a Parkinsonian disorder referred to as manganism.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
The Taub Institute for Research on Alzheimer's Disease and The Aging Brain, Columbia University, New York, NY, USA.
Background: At least one-third of the identified risk alleles from Genome Wide Association Studies of Alzheimer's disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. BIN1 which is also known as Amphiphysin 2; and PICALM which are involved in phosphoinositide metabolism and binding rank just below the highest risk gene variant of Apolipoprotein E (ApoEε4), a cholesterol and phospholipid transporter. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, CSF, blood and multiple mouse models of AD.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Background: Metabolomics offers promise in uncovering potential biomarkers and understanding the pathophysiology of autoimmune encephalitis (AE), which is a cluster of disorders with the host immune system targeting self-antigens expressed in the central nervous system (CNS). In this research, our objective was to explore metabolic characterization in cerebrospinal fluid (CSF) from individuals with AE, aiming to shed light on the pathophysiology of AE.
Methods: A targeted approach was applied using an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system to study CSF metabolites in patients with AE (n = 18), and control subjects without neurological diseases (n = 17).
Heliyon
November 2024
Food and Pharmacy College, Xuchang University, Xuchang, 461000, Henan, China.
Cyclin Dependent Kinase 1 (CDK1) plays a crucial role in cell cycle regulation, and dysregulation of its activity has been implicated in various cancers. Although several CDK1 inhibitors are currently in clinical trials, none have yet been approved for therapeutic use. This research utilized deep learning techniques, specifically Recurrent Neural Networks with Long Short-Term Memory (LSTM), to generate potential CDK1 inhibitors.
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