Search

Purpose: Many growth factors, such as fibroblast growth factors (FGFs), are useful for the treatment or prevention of radiation damage after radiation therapy. Although heparin can be supplemented to increase the therapeutic effects of FGFs, it possesses strong anticoagulant effects, which limit its potential for clinical use. Therefore, chemically sulfated hyaluronic acid (HA) was developed as a safe alternative to heparin. This study examined the involvement of sulfated HA in radioprotective and anticoagulant effects. Methods and Materials: FGF1 was administered intraperitoneally to BALB/c mice with sulfated HA 24 hours before or after total body irradiation with γ-rays. Several radioprotective effects were examined in the jejunum. The blood coagulation time in the presence of sulfated HA was measured using murine whole blood. Results: FGF1 with high-sulfated HA (HA-HS) exhibited almost the same level of in vitro mitogenic activity as heparin, whereas FGF1 with HA or low-sulfated HA exhibited almost no mitogenic activity. Furthermore, HA-HS had high binding capability with FGF1. FGF1 with HA-HS significantly promoted crypt survival to the same level as heparin after total body irradiation and reduced radiation-induced apoptosis in crypt cells. Moreover, pretreatment of HA-HS without FGF1 also increased crypt survival and reduced apoptosis. Crypt survival with FGF1 in the presence of HA depended on the extent of sulfation of HA. Moreover, the blood anticoagulant effects of sulfated HA were weaker than those of heparin. As sulfated HA did not promote the reactivity of antithrombin III to thrombin, it did not increase anticoagulative effects to the same extent as heparin. Conclusions: This study suggested that HA-HS promotes the radioprotective effects of FGF1 without anticoagulant effects. HA-HS has great potential for practical use to promote tissue regeneration after radiation damage.

O-GlcNAcylation is the only sugar modification for proteins present in the cytoplasm and nucleus and is thought to be involved in the regulation of protein function and localization. Currently, several methods are known for detecting O-GlcNAcylated proteins using monoclonal antibodies or wheat germ agglutinin, but these methods have some limitations in their sensitivity and quantitative comparison. We developed a new disaccharide-tag method to overcome these problems. This is a method in which a soluble GalNAc transferase is expressed intracellularly, extended to a disaccharide of GalNAc-GlcNAc, and detected using a Wisteria japonica agglutinin specific to this disaccharide. We verified the method using human c-Rel protein and also highly sensitively compared the difference in O-GlcNAc modification of intracellular proteins associated with differentiation from embryonic stem cell (ESC) to epiblast-like cells (EpiLC). As one example of such a modification, a novel O-GlcNAc modification was found in the transcription factor Sox2 at residue Ser263, and the modification site could be identified by nano liquid chromatography-mass spectrometry.

It is essential to clarify the characteristics of the material activation in cyclotron-type proton therapy facilities for future decommissioning. In particular, concrete occupies the largest volume among object materials, but its activation characteristics of activity level and distribution are unknown. We investigated concrete radioactivation in cyclotron-type proton therapy facilities at the National Cancer Center Hospital East and Aizawa Hospital. The in situ 24Na measurement method, which is easy and high sensitivity, was applied for the investigation. Using the in situ 24Na measurement method, we obtained the thermal neutron fluence rates in concrete with high sensitivity. Based on these fluence rates, the sum of the 152Eu and 60Co specific activities in the concrete were predicted for an operation duration of 30 years. The study aims to predict general 152Eu and 60Co (which are major radionuclides) specific activities for cyclotron-type proton therapy facilities, and we found the following common characteristics in the investigation results. In the accelerator room, neutrons were mainly produced at the degrader and/or objects surrounding it and diffused over the room. As a result, the sum of the ratios of the concrete floor's specific activities of 152Eu and 60Co for their respective clearance level (0.1 Bq/g) was estimated to be close to 1. On the other hand, the production of neutrons both in the treatment and beam transport line rooms was low, and the sum of the ratios of the 152Eu and 60Co specific activities for their respective clearance level was estimated to be below 1. [ABSTRACT FROM AUTHOR]