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A multi-kinase inhibitor screen identifies inhibitors preserving stem-cell-like chimeric antigen receptor T cells.
Nat Immunol
January 2025
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Chimeric antigen receptor T cells (CAR T cells) with T stem (T) cell-like phenotypic characteristics promote sustained antitumor effects. We performed an unbiased and automated high-throughput screen of a kinase-focused compound set to identify kinase inhibitors (KIs) that preserve human T cell-like CAR T cells. We identified three KIs, UNC10225387B, UNC10225263A and UNC10112761A, that combined in vitro increased the frequency of CD45RACCR7TCF1 T cell-like CAR T cells from both healthy donors and patients with cancer.
View Article and Find Full Text PDFYAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution.
Nat Commun
January 2025
Gleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego Health, La Jolla, CA, 92037, USA.
Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution.
View Article and Find Full Text PDFMicroRNA Profiling of PRELI-Modulated Exosomes and Effects on Hepatic Cancer Stem Cells.
Int J Mol Sci
December 2024
EVERBIO, 131, Jukhyeon-gil, Gwanghyewon-myeon, Jincheon-gun 27809, Republic of Korea.
The increasing incidence and mortality rates of liver cancer have heightened the demand for the development of effective anticancer drugs with minimal side effects. In this study, the roles of exosomes derived from liver cancer stem cells (LCSCs) with PRELI (Protein of Relevant Evolutionary and Lymphoid Interest) modulation and their miRNAs were investigated to explore their therapeutic properties for liver cancer. Various techniques, such as miRNA profiling, microRNA transfection, overexpression, flow cytometry, Western blotting, and immunocytochemistry, were used to evaluate the effects of exosomes under PRELI up- and downregulation.
View Article and Find Full Text PDFHarnessing Arsenic Derivatives and Natural Agents for Enhanced Glioblastoma Therapy.
Cells
December 2024
Laboratory of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado 350-0295, Saitama, Japan.
Glioblastoma (GBM) is the most common and lethal intracranial tumor in adults. Despite advances in the understanding of the molecular events responsible for disease development and progression, survival rates and mortality statistics for GBM patients have been virtually unchanged for decades and chemotherapeutic drugs used to treat GBM are limited. Arsenic derivatives, known as highly effective anticancer agents for leukemia therapy, has been demonstrated to exhibit cytocidal effects toward GBM cells by inducing cell death, cell cycle arrest, inhibition of migration/invasion, and angiogenesis.
View Article and Find Full Text PDFAntibody/siRNA Nanocarriers Against Wnt Signaling Suppress Oncogenic and Stem-Like Behavior in Triple-Negative Breast Cancer Cells.
J Biomed Mater Res A
January 2025
Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA.
Triple-negative breast cancer (TNBC) is infamous for its aggressive phenotype and poorer prognosis when compared to other breast cancer subtypes. One factor contributing to this poor prognosis is that TNBC lacks expression of the receptors that available hormonal or molecular-oriented therapies attack. New treatments that exploit biological targets specific to TNBC are desperately needed to improve patient outcomes.
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