Combination of cyclooxygenase-2 inhibitor and doxorubicin increases the growth inhibition and apoptosis in human hepatocellular carcinoma cells

Inhibition of cyclooxygenase (COX)-2 elicits therapeutic effects in solid tumors that are coupled with the inhibition of cell proliferation and induction of apoptosis in tumor cells. Aim: This study was designed to investigate the role of COX-2 inhibitor nimesulide in cell growth and apoptosis of the cultured human hepatocellular carcinoma HepG2 cells. Methods: We performed the MTT assay, flow cytometric analysis and cell morphology study to evaluate growth inhibition and cell apoptosis upon the action of nimesulide alone or along with doxorubicin, a common agent for the treatment of human hepatocellular carcinoma. Results: Our results showed that the treatment of HepG2 cells with more than 50 µM of nimesulide suppressed COX-2 enzyme activity because of reduced PGE2 production, and then induced growth inhibition and cell apoptosis despite no alterations of COX-2 protein expression. Importantly, the combination of 50 µM or 100 µM of nimesulide and low concentrations (5 µM to 20 µM) of doxorubicin resulted in enhanced cell growth inhibition, apoptosis induction and reduced VEGF production. Conclusion: These data suggest synergistic and/or additive effects of COX-2 inhibitors and chemotherapeutic agents, and may provide the rational for clinical studies of COX-2 inhibitors on the treatment or chemoprevention of human hepatocellular carcinoma.Угнетение циклооксигеназы-2 (ЦОГ-2) оказывает терапевтический эффект при лечении больных с солидными опухолями и сопровождается снижением пролиферации опухолевых клеток и индукцией апоптоза. Цель: изучение роли ингибитора ЦОГ-2 — нимесулида в процессах роста и апоптоза культивированных клеток гепатокарциномы человека HepG2. Методы: для оценки апоптоза и угнетения роста клеток при применении нимесулида самостоятельно и в сочетании с доксорубицином применяли MTT-анализ, проточную цитометрию и стандартные морфологические методы. Результаты: установлено, что обработка клеток HepG2 cells нимесулидом в концентрации > 50 μM приводила к угнетению активности ЦОГ-2 за счет снижения продукции PGE2 , после чего отмечали подавление роста и апоптоз клеток при неизмененном уровне экспрессии ЦОГ-2. Комбинированное применение 50 μM или 100 μM нимесулида и доксорубицина в концентрации 5–20 μM обусловило усиленное угнетение роста клеток, индукции апоптоза и снижение продукции VEGF. Выводы: полученные данные свидетельствуют о синергическом и/или аддитивном эффекте при применении ингибиторов ЦОГ-2 и химиотерапевтических препаратов

Electronic structure of fluorides: general trends for ground and excited state properties

The electronic structure of fluorite crystals are studied by means of density functional theory within the local density approximation for the exchange correlation energy. The ground-state electronic properties, which have been calculated for the cubic structures $CaF_{2}$,$SrF_{2}$, $BaF_{2}$, $CdF_{2}$, $HgF_{2}$, $\beta$-$PbF_{2}$, using a plane waves expansion of the wave functions, show good comparison with existing experimental data and previous theoretical results. The electronic density of states at the gap region for all the compounds and their energy-band structure have been calculated and compared with the existing data in the literature. General trends for the ground-state parameters, the electronic energy-bands and transition energies for all the fluorides considered are given and discussed in details. Moreover, for the first time results for $HgF_{2}$ have been presented

Progress on the Design of the Coupling coils for MICE andMUCOOL

The Muon Ionization Cooling Experiment (MICE) [1]willdemonstrate ionization cooling in a short section of a realistic coolingchannel using a muon beam at Rutherford Appleton Laboratory (RAL) in theUK. The MICE RF and Coupling Coil (RFCC) Module consists of asuperconducting solenoid mounted around four normal conducting 201.25-MHzRF cavities. The coil package that surrounds the RF cavities is to bemounted in a 1.4 m diameter vacuum vessel. The coupling coil confines thebeam in the RFCC module within the radius of the RF cavity beam windows.Each coupling magnet will be powered by a 300 A, 10 V power supply. Themaximum design longitudinal force that will be carried by the cold masssupport system is 0.5 MN. The detailed design and analysis of thecoupling magnet has been completed by ICST. The primary magnetic andmechanical design features of the coils are presented in thispaper

AC Losses in the MICE Channel Magnets -- Is This a Curse or a Blessing?

This report discusses the AC losses in the MICE channel magnets during magnet charging and discharging. This report talks about the three types of AC losses in the MICE magnets; the hysteretic AC loss in the superconductor, the coupling AC loss in the superconductor and the eddy current AC loss in the magnet mandrel and support structure. AC losses increase the heat load at 4 K. The added heat load increases the temperature of the second stage of the cooler. In addition, AC loss contributes to the temperature rise between the second stage cold head and the high field point of the magnet, which is usually close to the magnet hot spot. These are the curses of AC loss in the MICE magnet that can limit the rate at which the magnet can be charge or discharged. If one is willing to allow some of the helium that is around the magnet to boil away during a magnet charge or discharge, AC losses can become a blessing. The boil off helium from the AC losses can be used to cool the upper end of the HTS leads and the surrounding shield. The AC losses are presented for all three types of MICE magnets. The AC loss temperature drops within the coupling magnet are presented as an example of how both the curse and blessing of the AC losses can be combined

The Helium Cooling System and Cold Mass Support System for the MICE Coupling Solenoid

The MICE cooling channel consists of alternating three absorber focus coil module (AFC) and two RF coupling coil module (RFCC) where the process of muon cooling and reacceleration occurs. The RFCC module comprises a superconducting coupling solenoid mounted around four conventional conducting 201.25 MHz closed RF cavities and producing up to 2.2T magnetic field on the centerline. The coupling coil magnetic field is to produce a low muon beam beta function in order to keep the beam within the RF cavities. The magnet is to be built using commercial niobium titanium MRI conductors and cooled by pulse tube coolers that produce 1.5 W of cooling capacity at 4.2 K each. A self-centering support system is applied for the coupling magnet cold mass support, which is designed to carry a longitudinal force up to 500 kN. This report will describe the updated design for the MICE coupling magnet. The cold mass support system and helium cooling system are discussed in detail