Nitroreductase (NTR) is an endogenous reductase overexpressed in hypoxic tumors, with its levels closely correlated to the degree of hypoxia. This correlation has significant clinical implications for the analysis of tumor hypoxia, as it allows for the indirect detection of nitroreductases. Due to their simplicity, noninvasive nature, and excellent spatiotemporal resolution, various fluorescence methods have been developed for the analysis of nitroreductase and tumor hypoxia. In this study, we present the design, synthesis, in vitro evaluation, and biological application of an NTR-activated fluorescent probe, F-NTR. Utilizing an oxanthrene fluorophore as the core component, F-NTR incorporates a 4-nitrobenzene recognition group. This innovative probe, which introduces a nitro group, demonstrates high selectivity and reactivity towards nitroreductase (NTR) due to its reducing properties. Furthermore, probe F-NTR is capable of accurately identifying hypoxic environments, which provides a basis for precise detection and localization of tumors. This work lays the groundwork for future investigations into cell metabolism, tumor metabolism, and the surgical management of solid tumors under hypoxic conditions.
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http://dx.doi.org/10.1016/j.talanta.2025.127804 | DOI Listing |
Immune Netw
February 2025
Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
Regulatory T (Treg) cells are essential for maintaining immune homeostasis by suppressing excessive immune responses. In the context of cancer, however, Tregs promote immune evasion and tumor progression, particularly through their unique adaptations within the tumor microenvironment (TME). Recent research has emphasized how metabolic characteristics shape Treg activation, migration, and immunosuppressive function, revealing the impact of metabolic pathways on Treg fitness in homeostasis and within the TME.
View Article and Find Full Text PDFInt J Mol Sci
February 2025
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.
In MCF-7 breast cancer cells, transmembrane prostatic acid phosphatase (TM-PAP) plays a critical role in tumor progression, particularly under hypoxic conditions. In this study, the impact of hypoxia on ectophosphatase activity in MCF-7 cells was examined, and the underlying biological mechanisms that influence the breast cancer microenvironment were explored. Compared with normoxic cells, hypoxic cells presented significant reductions in ectophosphatase activity, indicating that hypoxia altered dephosphorylation processes critical for tumor growth and metastasis.
View Article and Find Full Text PDFCancers (Basel)
March 2025
Immun-Onkologisches Zentrum Köln, 50674 Köln, Germany.
Malignant glioma is a highly aggressive, therapeutically non-responsive, and deadly disease with a unique tumor microenvironment (TME). Of the 14 currently recognized and described cancer hallmarks, five are especially implicated in malignant glioma and targetable with repurposed drugs: cancer stem-like cells, in general, and glioma stem-like cells in particular (GSCs), vascularization and hypoxia, metabolic reprogramming, tumor-promoting inflammation and sustained proliferative signaling. Each hallmark drives malignant glioma development, both individually and through interactions with other hallmarks, in which the TME plays a critical role.
View Article and Find Full Text PDFCancers (Basel)
March 2025
Department of Surgery, University of Southern California, Los Angeles, CA 90089, USA.
Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to its dense fibrotic stroma that promotes drug resistance and tumor progression. While patient-derived organoids (PDOs) have emerged as promising tools for modeling PDAC and evaluating therapeutic responses, the current PDO models grown in soft matrices fail to replicate the tumor's stiff extracellular matrix (ECM), limiting their predictive value for advanced disease.
Methods: We developed a biomimetic model using gelatin-based matrices of varying stiffness, achieved through modulated transglutaminase crosslinking rates, to better simulate the desmoplastic PDAC microenvironment.
Fluids Barriers CNS
March 2025
Department of Physiology, College of Medicine, Kuwait University, P.O. Box 24923, 13110, Safat, Kuwait.
Background: Hypoxemia can cause secondary acute brain injury, but the mechanisms behind it are not entirely clear and could involve disturbances in the brain extracellular fluids. We aimed to explore the effects of hypoxemia on the choroid plexus (CPs) and cerebrospinal fluid (CSF) system in rats.
Methods: Male Sprague Dawley rats were kept in O control in vivo cabinet with either 21% (normoxia) or 8% O (hypoxemia) for up to 48 h.
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