The synthesis and full characterization of new half-sandwich ruthenium(II) complexes containing κ(3)(N,N,N)-hydridotris(pyrazolyl)borate (κ(3)(N,N,N)-Tp) and the water-soluble phosphanes 1,3,5-triaza-7-phosphatricyclo[3.3.1.1(3,7)]decane (PTA) and 1-methyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1(3,7)]decane (1-CH(3)-PTA) has been explored. Single crystal X-ray diffraction analysis for complex [RuCl{κ(3)(N,N,N)-Tp}(PMe(2)Ph)(1-CH(3)-PTA)][CF(3)SO(3)]·2NCMe is also reported. DNA binding properties of the ruthenium complexes have been evaluated by mobility shift assay and MALDI-TOF mass spectrometry. The in vitro antitumor activity of these compounds was assessed by examining their ability to inhibit cell proliferation in a number of human cancer cell lines (NCI-H460, SF-268, MCF-7) and non-tumor human umbilical vein endothelial cells (HUVEC). Some of these new compounds show promising cytotoxic activity with IC(50) values in the low micromolar range, and display differential effects on cancer and normal cell growth.
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http://dx.doi.org/10.1039/c0dt00206b | DOI Listing |
Angew Chem Int Ed Engl
January 2025
University of Chicago Division of the Physical Sciences, chemistry, UNITED STATES OF AMERICA.
Immune checkpoint blockade (ICB) has revolutionized the treatment of many cancers by leveraging the immune system to combat malignancies. However, its efficacy is limited by the immunosuppressive tumor microenvironment and other regulatory mechanisms of the immune system. Innate immune modulators (IIMs) provide potent immune activation to complement adaptive immune responses and help overcome resistance to ICB.
View Article and Find Full Text PDFSci Immunol
January 2025
Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2.
View Article and Find Full Text PDFCell Rep
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) molecules retains the class II-associated invariant chain peptide (CLIP) fragment of the invariant chain bound to the MHC-II peptide binding groove due to reduced expression of the peptide editor H2-M and enhanced activity of the CLIP-generating proteinase cathepsin S. The net effect of this is that MHC-II molecules are unable to efficiently bind antigenic peptides.
View Article and Find Full Text PDFCancer Immunol Immunother
January 2025
Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.
The combined use of tocilizumab (TCZ) and immune checkpoint inhibitors (ICIs) in cancer treatment is gaining attention, but preclinical studies are lacking. Our study aims to investigate the synergistic anti-tumor effect of TCZ combined with ICIs and its role in treating immune-related adverse events (irAEs). The clinical significance of high interleukin-6 (IL-6) expression in tumor patients was analyzed from the Cancer Genome Atlas (TCGA) database.
View Article and Find Full Text PDFCancer Immunol Immunother
January 2025
Department of Oncology, Lianyungang Clinical College of Nanjing Medical University/The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, China.
Background: Due to its strong immunogenicity and tumor specificity, neoplastic antigen has emerged as an immunotherapy target with wide therapeutic prospect and clinical application value. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. So, we conducted single-arm trial to assess the safety and efficacy of PD-1 blockade(Camrelizumab)-activated neoantigen specific cellular therapy (aNASCT) on advanced relapsed non-small lung cancer(NSCLC)(ClinicalTrials.
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