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Disitamab vedotin in preclinical models of HER2-positive breast and gastric cancers resistant to trastuzumab emtansine and trastuzumab deruxtecan.
Transl Oncol
January 2025
Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Laboratory of Molecular Oncology, Biomedicum, University of Helsinki, Helsinki, Finland. Electronic address:
Background: Most HER2-positive breast or gastric cancers eventually become resistant to the approved anti-HER2 antibody-drug conjugates (ADC) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). Disitamab vedotin (DV) is a novel anti-HER2 ADC that binds to a different epitope on HER2 compared to trastuzumab. We assessed the efficacy of DV in breast and gastric cancer cell lines and xenografts, including tumor models resistant to T-DM1 and T-DXd.
View Article and Find Full Text PDFRole of cardiolipin in skeletal muscle function and its therapeutic implications.
Cell Commun Signal
January 2025
Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
Cardiolipin, a unique phospholipid predominantly present in the inner mitochondrial membrane, is critical for maintaining mitochondrial integrity and function. Its dimeric structure and role in supporting mitochondrial dynamics, energy production, and mitophagy make it indispensable for skeletal muscle health. This review provides a comprehensive overview of cardiolipin biosynthesis, remodeling processes, and essential functions within mitochondria.
View Article and Find Full Text PDFNeuronal excitation-transcription (E-T) coupling pathways can be initiated by local increases of Ca concentrations within a nanodomain close to the L-type voltage-gated Ca channel (LTCC). However, molecular mechanisms controlling LTCC organization within the plasma membrane that help creation these localized signaling domains remain poorly characterized. Here, we report that neuronal depolarization increases Ca 1.
View Article and Find Full Text PDFIntegrins are a large family of heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1, also known as the fibronectin receptor, is a key mediator of angiogenesis and its dysregulation is associated with tumor proliferation, progression, and metastasis. Despite numerous efforts, α5β1-targeting therapeutics have been unsuccessful in large part due to efficacy and off-target effects.
View Article and Find Full Text PDFStructural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS.
Nat Commun
January 2025
Department of Pharmacology, Yale University School of Medicine, New Haven, CT, 06520, USA.
Sevenless, the Drosophila homologue of ROS1 (University of Rochester Sarcoma) (herein, dROS1) is a receptor tyrosine kinase (RTK) essential for the differentiation of Drosophila R7 photoreceptor cells. Activation of dROS1 is mediated by binding to the extracellular region (ECR) of the GPCR (G protein coupled receptor) BOSS (Bride Of Sevenless) on adjacent cells. Activation of dROS1 by BOSS leads to subsequent downstream signaling pathways including SOS (Son of Sevenless).
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