Imaging of Hydroxyl-Radical Generation Using Dynamic Nuclear Polarization-Magnetic Resonance Imaging and a Spin-Trapping Agent.

Reactive oxygen species (ROS) play an important role in cell metabolism, but they can cause oxidative damage to biomolecules. Among ROS, the hydroxyl radical (·OH) is one of the most reactive molecules in biological systems because of its high reaction rate constant. Therefore, imaging of ·OH could be useful for evaluation of the redox mechanism and diagnosis of oxidative diseases.

The antibodies against 5-bromo-2'-deoxyuridine specifically recognize trifluridine incorporated into DNA.

Trifluridine (FTD) is a key component of the novel oral antitumor drug TAS-102 (also named TFTD), which consists of FTD and a thymidine phosphorylase inhibitor. FTD is supposed to exert its cytotoxicity via massive misincorporation into DNA, but the underlying mechanism of FTD incorporation into DNA and its correlation with cytotoxicity are not fully understood. The present study shows that several antibodies against 5-bromo-2'-deoxyuridine (BrdU) specifically cross-react with FTD, either anchored to bovine serum albumin or incorporated into DNA.

Redox imaging of skeletal muscle using in vivo DNP-MRI and its application to an animal model of local inflammation.

Disorders of skeletal muscle are often associated with inflammation and alterations in redox status. A non-invasive technique that could localize and evaluate the severity of skeletal muscle inflammation based on its redox environment would be useful for disease identification and monitoring, and for the development of treatments; however, no such technique currently exists. We describe a method for redox imaging of skeletal muscle using dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), and apply this method to an animal model of local inflammation.

Trifluridine Induces p53-Dependent Sustained G2 Phase Arrest with Its Massive Misincorporation into DNA and Few DNA Strand Breaks.

Trifluridine (FTD) is a key component of the novel oral antitumor drug TAS-102, which consists of FTD and a thymidine phosphorylase inhibitor. Like 5-fluoro-2'-deoxyuridine (FdUrd), a deoxynucleoside form of 5-fluorouracil metabolite, FTD is sequentially phosphorylated and not only inhibits thymidylate synthase activity, but is also incorporated into DNA. Although TAS-102 was effective for the treatment of refractory metastatic colorectal cancer in clinical trials, the mechanism of FTD-induced cytotoxicity is not completely understood.