Anti-tumor activity of BET inhibitors in androgen-receptor-expressing triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous disease comprising several subtypes. Androgen-receptor (AR) signaling has been targeted by several investigational agents in luminal AR subtype TNBCs. Bromodomain (BRD) and extra-terminal motif (BET) protein inhibitors have been shown to attenuate AR signaling in metastatic castration-resistant prostate cancer and to overcome enzalutamide resistance. We demonstrated potent anti-tumor effects of the BET inhibitor JQ1 against AR-positive TNBC cell lines using cell viability and cell cycle analysis. To reveal the mechanisms of JQ1 effects, multiplex gene expression analysis and immunoblotting assays were used. We examined in vivo effects of JQ1 in a xenograft model of AR expressing TNBC. JQ1 exhibited its anti-proliferative activity by inducing apoptosis and cell cycle arrest. JQ1 activity was not mediated by MYC downregulation. Instead, JQ1 blocked the interactions among the ATPase-family AAA-domain-containing 2 protein (ATAD2), BRD2, BRD4, and AR; effectively suppressing the expression of AR associated targets. In addition, JQ1 showed significant anti-tumor activity in vivo in TNBC xenograft mouse models as a monotherapy and in combination with anti-AR therapy. Taken together, our results showed that the BET inhibitor JQ1 is a promising therapeutic agent for the treatment of AR-positive TNBC.

Nitrogen oxides emissions from the MILD combustion with the conditions of recirculation gas.

The nitrogen oxides (NOx) reduction technology by combustion modification which has economic benefits as a method of controlling NOx emitted in the combustion process, has recently been receiving a lot of attention. Especially, the moderate or intense low oxygen dilution (MILD) combustion which applied high temperature flue gas recirculation has been confirmed for its effectiveness with regard to solid fuel as well. MILD combustion is affected by the flue gas recirculation ratio and the composition of recirculation gas, so its NOx reduction efficiency is determined by them. In order to investigate the influence of factors which determine the reduction efficiency of NOx in MILD coal combustion, this study changed the flow rate and concentration of nitrogen (N2), carbon dioxide (CO2) and steam (H2O) which simulate the recirculation gas during the MILD coal combustion using our lab-scale drop tube furnace and performed the combustion experiment. As a result, its influence by the composition of recirculation gas was insignificant and it was shown that flue gas recirculation ratio influences the change of NOx concentration greatly. IMPLICATIONS: We investigated the influence of factors determining the nitrogen oxides (NOx) reduction efficiency in MILD coal combustion, which applied high-temperature flue gas recirculation. Using a lab-scale drop tube furnace and simulated recirculation gas, we conducted combustion testing changing the recirculation gas conditions. We found that the flue gas recirculation ratio influences the reduction of NOx emissions the most.

Low-nitrogen oxides combustion of dried sludge using a pilot-scale cyclone combustor with recirculation.

UNLABELLED: Recently, numerical and experimental studies have been conducted to develop a moderate or intense low-oxygen dilution (MILD) combustion technology for solid fuels. The study results demonstrated that intense recirculation inside the furnace by high-momentum air is a key parameter to achieve the MILD combustion of solid fuels. However, the high-velocity air requires a significant amount of electricity consumption. A cyclone-type MILD combustor was therefore designed and constructed in the authors' laboratory to improve the recirculation inside the combustor. The laboratory-scale tests yielded promising results for the MILD combustion of dried sewage sludge. To achieve pilot-scale MILD combustion of dried sludge in this study, the effects of geometric parameters such as the venturi tube configuration, the air injection location, and the air nozzle diameter were investigated. With the optimized geometric and operational conditions, the pilot-scale cyclone combustor demonstrated successful MILD combustion of dried sludge at a rate of 75 kg/hr with an excess air ratio of 1.05. IMPLICATIONS: A horizontal cyclone combustor with recirculation demonstrated moderate or intense low-oxygen dilution (MILD) combustion of dried sewage sludge at a rate of 75 kg/hr. Optimizing only geometric and operational conditions of the combustor reduced nitrogen oxide (NOx) emissions to less than 75 ppm. Because the operating cost of the MILD combustor is much lower than that of the selective catalytic reduction (SCR) applied to the conventional combustor, MILD combustion technology with the cyclone type furnace is an eligible option for reducing NOx emissions from the combustion of dried sewage sludge.