Improvement of resistance to oxaliplatin by vorinostat in human colorectal cancer cells through inhibition of Nrf2 nuclear translocation.

Vorinostat (suberoylanilide hydroxamic acid: SAHA), a histone deacetylase inhibitor, has potential benefit of improving the resistance to conventional other anti-cancer drugs. This study was aimed to clarify whether SAHA improves the resistance to oxaliplatin (L-OHP), a platinum-based anticancer drug using L-OHP-resistant HCT116 cells (HCT116/OxR), established from colorectal cancer (CRC) cell line HCT116. HCT116/OxR cells showed cross-resistance to other platinum-based drugs. Pre-treatment with SAHA improved the sensitivity of both L-OHP and its metabolite in HCT116/OxR cells, but not in parental HCT116 cells. However, pre-treatment with SAHA did not affect the sensitivity of other platinum-based drugs. These results indicated that SAHA specifically improved the sensitivity of L-OHP in HCT116/OxR cells. Focusing on NF-E2 p45-related factor 2-Kelch-like ECH-associated protein 1 pathway (Nrf2-Keap1) pathway, which is activated by oxidative stress such as the treatment with anti-cancer drugs, mechanisms behind these observations were elucidated. In HCT116/OxR cells transfected with Nrf2 siRNA, the improving effects on L-OHP resistance by SAHA were abolished, suggesting that Nrf2-Keap1 pathway was involved in L-OHP-resistance. In addition, L-OHP metabolite significantly induced the expression of the nuclear protein Nrf2 and its target gene mRNA expression in HCT116/OxR cells. Pre-treatment with SAHA suppressed these changes observed in HCT116/OxR cells. In conclusion, this study demonstrated that SAHA improved L-OHP resistance by inhibiting Nrf2-Keap1 activation via Nrf2 nuclear translocation by L-OHP metabolite.

Aerodynamic levitator for large-sized glassy material production.

Containerless aerodynamic levitation processing is a unique technology for the fabrication of bulk non-crystalline materials. Using conventional aerodynamic levitation, a high reflective index (RI) material (BaTi2O5 and LaO3/2-TiO2-ZrO2 system) was developed with a RI greater than approximately 2.2, which is similar to that of diamond. However, the glass size was small, approximately 3 mm in diameter. Therefore, it is essential to produce large sized materials for future optical materials applications, such as camera lenses. In this study, a new aerodynamic levitator was designed to produce non-crystalline materials with diameters larger than 6 mm. The concept of this new levitator was to set up a reduced pressure at the top of the molten samples without generating turbulent flow. A numerical simulation was also performed to verify the concept.

A microgravity experiment of the on-orbit fluid transfer technique using swirl flow.

The cryogenic fluid transfer technique will prove useful for flexible and low-cost space activities by prolonging the life cycle of satellites, orbital transfer vehicles, and orbital telescopes that employ cryogenic fluids, such as reactants, coolants, and propellants. Although NASA has conducted extensive research on this technique to date, a complicated mechanism is required to control the pressure in the receiver tank and avoid a large liquid loss by vaporization. We have proposed a novel fluid transfer method by using swirl flow combined with vapor condensation facilitated by spray cooling. This technique enables gas-liquid separation in microgravity and effectively facilitates vapor condensation without any special device like a mixer. In addition, since the incoming liquid flows along the tank wall, the tank wall would be cooled effectively, thereby minimizing the liquid loss due to vaporization. In this paper, the influence of the number of inlet points, fluid velocity at the inlet, fluid type, and boiling condition on swirl flow under microgravity conditions is investigated experimentally. The results indicated that the new fluid transfer technique using the swirl flow proposed by us is effective for cryogenic fluids that generally exhibit low surface tension and good wettability. In addition, it is possible to apply this technique to the real system because the swirl flow conditions are determined by the Froude number, which is dimensionless. Thus, the fundamental technique of fluid transfer by using the swirl flow under microgravity conditions was established.