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Physiological functions of calcium signaling via Orai1 in cancer.
J Physiol Sci
January 2025
Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. Electronic address:
Intracellular calcium (Ca) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca entry (SOCE) is a major mechanism by which Ca is imported from the extracellular space to the intracellular space, especially in nonexcitable cells. Store-operated Ca entry (SOCE) is also a receptor-regulated Ca entry pathway that maintains Ca homeostasis by sensing reduced Ca levels in the endoplasmic reticulum (ER).
View Article and Find Full Text PDFDesign, Synthesis, and SAR of Covalent KIT and PDGFRA Inhibitors─Exploring Their Potential in Targeting GIST.
J Med Chem
January 2025
Department of Chemistry and Chemical Biology, TU Dortmund University and Drug Discovery Hub Dortmund (DDHD), Zentrum für Integrierte Wirkstoffforschung (ZIW), Otto-Hahn-Strasse 4a, Dortmund 44227, Germany.
Gastrointestinal stromal tumors (GIST), driven by KIT and PDGFRA mutations, are the most common mesenchymal tumors of the gastrointestinal tract. Although tyrosine kinase inhibitors (TKIs) have advanced treatment, resistance mutations and off-target toxicity limit their efficacy. This study develops covalent TKIs targeting drug-resistant GIST through structure-based design, synthesis, and biological evaluation.
View Article and Find Full Text PDFMyelodysplastic syndromes (MDS) are age-related diseases characterized by bone marrow (BM) dysfunction and an increased risk of developing acute leukemia. While there is growing evidence highlighting the crucial role of the BM microenvironment (BMME) in MDS, the specific influence of inflammation on BMME changes, as well as the potential benefits of targeting cytokines therapeutically, remain to be elucidated. We previously found interleukin-1 (IL-1) to be a driver of aging phenotypes of BMME and hematopoietic stem and progenitor cells (HSPCs).
View Article and Find Full Text PDFBioprinted Fibroblast Mediated Heterogeneous Tumor Microenvironment for Studying Tumor-Stroma Interaction and Drug Screening.
Adv Healthc Mater
January 2025
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Guangming District, Shenzhen, Guangdong, 518107, China.
Cancer-associated fibroblasts (CAFs) are crucial stromal cells in the tumor microenvironment, affecting cancer growth, angiogenesis, and matrix remodeling. Developing an effective in vitro tumor model that accurately recapitulates the dynamic interplay between tumor and stromal cells remains a challenge. In this study, a 3D bioprinted fibroblast - mediated heterogeneous breast tumor model was created, with tumor cells and fibroblasts in a bionic matrix.
View Article and Find Full Text PDFMacrophages in sepsis-induced acute lung injury: exosomal modulation and therapeutic potential.
Front Immunol
January 2025
Department of Critical Care Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
Sepsis-induced acute lung injury (ALI) remains a leading cause of mortality in critically ill patients. Macrophages, key modulators of immune responses, play a dual role in both promoting and resolving inflammation. Exosomes, small extracellular vesicles released by various cells, carry bioactive molecules that influence macrophage polarization and immune responses.
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