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Current perspectives and the future of disease-modifying therapies in type 1 diabetes.
World J Diabetes
January 2025
Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom.
Use of immunomodulating agents to prevent the progression of autoimmune β-cell damage leading to type 1 diabetes mellitus (T1DM) is an interesting area for research. These include non-specific anti-inflammatory agents, immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines. Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.
View Article and Find Full Text PDFPhytosome-Enhanced Secondary Metabolites for Improved Anticancer Efficacy: Mechanisms and Bioavailability Review.
Drug Des Devel Ther
January 2025
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia.
Purpose: Phytosome technology, an advanced lipid-based delivery system, offers a promising solution for enhancing the bioavailability and therapeutic efficacy of secondary metabolites, particularly in cancer treatment. These metabolites, such as flavonoids, terpenoids, and alkaloids, possess significant anticancer potential but are often limited by poor solubility and low absorption. This review aims to investigate how phytosome encapsulation improves the pharmacokinetic profiles and anticancer effectiveness of these bioactive compounds.
View Article and Find Full Text PDFNew Potent Inhibitor of Transforming Growth Factor-Beta (TGFβ) Signaling that is Efficacious against Microsatellite Stable Colorectal Cancer Metastasis in Combination with Immune Checkpoint Therapy in Mice.
ACS Pharmacol Transl Sci
January 2025
Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, Barcelona 08028, Spain.
Blockade of the TGFβ signaling pathway has emerged from preclinical studies as a potential treatment to enhance the efficacy of immune checkpoint inhibition in advanced colorectal cancer (CRC) and several other types of cancer. However, clinical translation of first-generation inhibitors has shown little success. Here, we report the synthesis and characterization of HYL001, a potent inhibitor of TGFβ receptor 1 (ALK5), that is approximately 9 times more efficacious than the structurally related compound galunisertib, while maintaining a favorable safety profile.
View Article and Find Full Text PDFSignatures of H3K4me3 modification predict cancer immunotherapy response and identify a new immune checkpoint-SLAMF9.
Respir Res
January 2025
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
H3 lysine 4 trimethylation (H3K4me3) modification and related regulators extensively regulate various crucial transcriptional courses in health and disease. However, the regulatory relationship between H3K4me3 modification and anti-tumor immunity has not been fully elucidated. We identified 72 independent prognostic genes of lung adenocarcinoma (LUAD) whose transcriptional expression were closely correlated with known 27 H3K4me3 regulators.
View Article and Find Full Text PDFThe translational landscape of HIV-1 infected cells reveals key gene regulatory principles.
Nat Struct Mol Biol
January 2025
Helmholtz Institute for RNA-based Infection Research, Helmholtz Centre for Infection Research (HIRI-HZI), Würzburg, Germany.
Human immunodeficiency virus-1 (HIV-1) uses a number of strategies to modulate viral and host gene expression during its life cycle. To characterize the transcriptional and translational landscape of HIV-1 infected cells, we used a combination of ribosome profiling, disome sequencing and RNA sequencing. We show that HIV-1 messenger RNAs are efficiently translated at all stages of infection, despite evidence for a substantial decrease in the translational efficiency of host genes that are implicated in host cell translation.
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