Synthesis of fluorocyclopentenyl pyrimidine nucleosides 6-9 was enantiopurely accomplished employing oxidative rearrangement, RCM reaction and electrophilic fluorination starting from d-ribose. Cytosine analog 8 was found to exhibit significant anticancer activity in various human tumor cell lines.
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http://dx.doi.org/10.1080/15257770701490852 | DOI Listing |
Sci Rep
January 2025
Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University, (Third Military Medical University), Chongqing, China.
Acute kidney injury (AKI) has become a disease of global concern due to its high morbidity and mortality. This has highlighted the need for renoprotective agents. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus with good antioxidant, anti-inflammatory and anti-tumor properties.
View Article and Find Full Text PDFCommun Biol
January 2025
Protein Interactome Laboratory for Structural and Functional Biology, Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai, India.
Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity.
View Article and Find Full Text PDFNat Commun
January 2025
Carisma Therapeutics Inc, Philadelphia, PA, USA.
We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
The efficacy of cancer immunotherapy relies on a sufficient amount of functional immune cells. Triple-negative breast cancer lacks enough immune cell infiltration, and adjuvant therapy is necessary to prime anti-tumor immunity. However, the improvement in efficacy is unsatisfactory with concern about inducing systemic immunotoxicity.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Changchun Institute of Applied Chemistry Chinese Academy of Sciences: Chang Chun Institute of Applied Chemistry Chinese Academy of Sciences, State Key Laboratory of Rare Earth Resource Utilization, CHINA.
Tumor immunotherapy has been widely used clinically, but it is still hindered by weak antitumor immunity and immunosuppressive tumor microenvironment (TME). Here, a kind of simple disodium hydrogen phosphate nanoparticle (Na2HPO4 NP) is prepared to "accelerate" tumor immunotherapy by "increasing throttle" and "relaxing brake" simultaneously. The obtained Na2HPO4 NPs release a large amount of Na+ and HPO42- ions within tumor cells, thereby activating the caspase 1/GSDMD-mediated pyroptosis pathway to achieve immune activation.
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