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Tumor hypoxia renders treatments ineffective that are directly (e.g., radiotherapy and photodynamic therapy) or indirectly (e.g., chemotherapy) dependent on tumor oxygenation. This study introduces a ruthenium compound as a light-responsive anticancer agent that is water-soluble, has minimal dark cytotoxicity, is active at concentrations as low as 170 pM in ∼18.5% O normoxia and near 10 nM in 1% O hypoxia, and exhibits phototherapeutic indices as large as >500,000 in normoxia and >5,800 in 1% O hypoxia using broadband visible and monochromatic blue light treatments. These are the largest values reported to date for any compound class. We highlight the response in four different cell lines to improve rigor and reproducibility in the identification of promising clinical candidates.
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http://dx.doi.org/10.1021/jacs.1c09010 | DOI Listing |
JCO Precis Oncol
September 2025
Division of Hematology and Oncology, University of California Los Angeles, Los Angeles, CA.
Purpose: mutations are classically seen in non-small cell lung cancers (NSCLCs), and EGFR-directed inhibitors have changed the therapeutic landscape in patients with -mutated NSCLC. The real-world prevalence of -mutated ovarian cancers has not been previously described. We aim to determine the prevalence of pathogenic or likely pathogenic mutations in ovarian cancer and describe a case of -mutated metastatic ovarian cancer with a durable response to osimertinib, an EGFR-directed targeted therapy.
View Article and Find Full Text PDFPLoS One
September 2025
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Crosstalk between leukemic cells and their surrounding mesenchymal stromal cells (MSCs) in the bone marrow microenvironment is crucial for the pathogenesis of myelodysplastic syndromes (MDS) and is mediated by extracellular vesicles (EVs). The EV-specific miRNAs derived from MDS-MSCs remain poorly explored. EVs isolated from HS-5, an immortalized stromal cell line, promoted the proliferation and 5-azacytidine (AZA) resistance of SKM-1 cells.
View Article and Find Full Text PDFSci Adv
September 2025
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
(phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including , , , and , even in the absence of IFN-γ stimulation in vitro.
View Article and Find Full Text PDFSci Transl Med
September 2025
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.
Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8 T cells in early TNBC samples, which predict immunotherapy nonresponsiveness.
View Article and Find Full Text PDFSci Transl Med
September 2025
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
IFN-β, a type I interferon, has been used as a first-line therapy for patients with multiple sclerosis (MS) for more than 30 years; however, the cellular and molecular basis of its therapeutic efficacy remains unclear. Here, we first used experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, to show that the therapeutic effects of IFN-β were associated with a down-regulation of microRNA-21 (miR-21) and pathogenic T17 (pT17) cells. In vitro experiments demonstrated that genetic knockout of miR-21 directly inhibited pathogenic T17 cell differentiation.
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