TONS504-PHOTODYNAMIC THERAPY INDUCES CYTOTOXIC EFFECTS IN EMT6 CELLS

In the present study, TONS504 (C51H58N8O5I2; molecular weight, 1,116.9), a novel cationic hydrophilic photosensitizer, was synthesized from protoporphyrin IX dimethyl ester through a five‑step process according to a patented method for use in photodynamic therapy (PDT). The subcellular localization of TONS504 and the cytotoxic effects of TONS504‑mediated PDT in the mouse mammary tumor EMT6 cell line were investigated. TONS504 was localized primarily in the lysosomes and partially in the mitochondria. The cytotoxic effects of TONS504‑mediated PDT in the mouse mammary tumor EMT6 cell line were investigated using a WST8 assay and an Oxidative Stress kit. The cell viability values following treatment with 10 µg/ml TONS504 at light energies of 0, 1, 5 and 10 J/cm2 were 92.5, 101.8, 27.7 and 1.8%, respectively. The percentages of reactive oxygen species (ROS)(+) cells following the same treatment were 8.6, 8.5, 29.2 and 70.1%, respectively, whereas the percentages of apoptotic cells were 7.1, 5.6, 24.8 and 48.7%, respectively. The percentages of ROS(+) and apoptotic cells in the group subjected to TONS504‑mediated PDT increased in a manner dependent on the TONS504 concentration and light energy. Further studies are required to evaluate the in vivo pharmacokinetics, tissue distribution and photodynamic effects of TONS504

Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro

Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required

Investigation of the Utility and Safety of Dynamic Computed Tomography with Vasodilators

Background: Dynamic computed tomography (CT) angiography is useful for evaluating of hepatic vascularity. Although vasodilators increase hepatic blood flow, the utility of dynamic CT with vasodilators is unclear. Here we investigated the utility and safety of dynamic CT with vasodilators. Methods: A prospective case-control radiographic evaluation using abdominal dynamic CT with and without vasodilator was performed at a single center between October 2015 and September 2016. We compared the CT values in Hounsfield units of the aorta; celiac artery; and common, right, and left hepatic arteries in the arterial phase and the main trunk; right and left branches of the portal vein; and right, middle, and left hepatic veins in the portal phase with and without vasodilators. The region of interest was set in each element of the liver vasculature. Four radiological technologists independently and visually compared the scores of the portal vein (P-score) and hepatic vein (V-score) on a 5-point scale with and without vasodilators. Results: The CT values of arteries and veins using vasodilators were significantly higher than those without vasodilators. With and without vasodilators, the P-scores were 3.1 ± 1.2 and 4.0 ± 1.1 (P < 0.05) and the V-scores were 3.3 ± 1.4 and 4.3 ± 1.0 (P < 0.05). Only one patient with vasodilator use had transient hypotension and recovered immediately without medication. Conclusion: Dynamic CT with vasodilators can provides better visualization of vascular structures

Effects of Oral Glucosamine Hydrochloride Administration on Plasma Free Amino Acid Concentrations in Dogs

We examined the effects of oral glucosamine hydrochloride (GlcN), N-acetyl-d-glucosamine (GlcNAc) and d-glucose (Glc) administration on plasma total free amino acid (PFAA) concentrations in dogs. The PFAA concentrations increased in the control group and the GlcNAc group at one hour after feeding, and each amino acid concentration increased. On the other hand, in the GlcN group and the Glc group PFAA concentrations decreased at one hour after feeding. A significant decrease in amino acid concentration was observed for glutamate, glycine and alanine. Our results suggest the existence of differences in PFAA dynamics after oral administration of GlcN and GlcNAc in dogs