Glutaminase 1 inhibition reduces thymidine synthesis in NSCLC

AbstractWe found that non-small cell lung cancer (NSCLC) is remarkably sensitive to the regulation of glutamine supply by testing the metabolic dependency of 11 cancer cell lines against regulation of glycolysis, autophagy, fatty acid synthesis, and glutamine supply. Glutamine is known as a key supplement of cancer cell growth that is converted to α-ketoglutarate for anabolic biogenesis via glutamate by glutaminase 1 (GLS1). GLS1 inhibition using 10 μM of bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) showed about 50% cell growth arrest by SRB assay. By testing the synergistic effects of conventional therapeutics, BPTES combined with 5-fluorouracil (5-FU), an irreversible inhibitor of thymidylate synthase, significant effects were observed on cell growth arrest in NSCLC. We found that GLS1 inhibition using BPTES reduced metabolic intermediates including thymidine and carbamoyl phosphate. Reduction of thymidine and carbamoyl-phosphate synthesis by BPTES treatment exacerbated pyrimidine supply by combination with 5-FU, which induced cell death synergistically in NSCLC

CO-COMBUSTION OF KOREAN ANTHRACITE WITH VARIOUS FUELS IN A COMMERCIAL CIRCULATING FLUIDIZED BED BOILER

The effect of co-combustion of various fuels such as bituminous coal, imported anthracite, RDF and wood pellet with Korean anthracite on the combustion and environmental performance was observed in the commercial CFB boiler. The temperatures in the furnace and cyclones exits decreased with increasing the cocombustion ratio of the bituminous coal, which could achieve more stable operation of the CFB boiler. During Co-combustion of the RDF and wood pellets, the temperature of the furnace exit increased slightly with due to volatiles re-combustion which could restrict to increase the co-combustion ratio of the RDF and wood pellets in the CFB boiler. It was limited for the electrostatic precipitator (EP) to maintain the stable operation above 5% of the RDF co-combustion ratio according to decrease of the output voltages of the EP collecting plate. High content of CaO in the RDF and the wood pellet made the required limestone flow rates decrease. The emissions NOx, HCl and dioxin during co-combustion of the RDF and wood pellets did not change appreciably when compared with firing only Korean anthracite, which were also low enough to meet Korean regulation limits. On the other hand, chlorine content in the ashes emitted from the boiler increased gradually with increasing the RDF co-combustion ratio because of absorption by limestone. The co-combustion of various fuels with Korean anthracite in the commercial CFB boiler was found to be of great use up to a certain co-combustion ratio of each fuel without the technical and environmental problems

Antioxidant effect of lidocaine and procaine on reactive oxygen species-induced endothelial dysfunction in the rabbit abdominal aorta

Background: Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in the endothelium. We tested the antioxidant effect of lidocaine and procaine on ROS-induced endothelial damage in the rabbit aorta. Methods: Aortic rings isolated from rabbits were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O 2 at 37.5??C. After precontraction with phenylephrine (PE, 10 -6 M), changes in tension were recorded following a cumulative administration of acetylcholine (ACh 3 ?? 10-8 to 10 -6 M). Differences were measured as percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS as generated by electrolysis of the K-H solution. The aortic rings were pretreated with lidocaine or procaine (10-5 M to 3 ?? 10-3 M) to compare their effects, as well as ROS scavengers, catalase, mannitol, sodium salicylate, and deferoxamine, and a catalase inhibitor, 3-amino-1,2,4-triazole (3AT). Results: Lidocaine and procaine dose-dependently maintained endothelium-dependent relaxation induced by ACh despite ROS activity (P < 0.05 vs control value). The 3AT pretreated procaine (3 ?? 10-3 M) group decreased more significantly than the un-pretreated procaine group (P < 0.05). Conclusions: These findings suggest that lidocaine and procaine dose-dependently preserve endothelium-dependent vasorelaxation against ROS attack, potentially via hydrogen peroxide scavenging. Copyright ?? Korean Society of Anesthesiologists, 2010

Teatro e ensino da matemática: atividade desenvolvida num curso de formação docente

Anais do II Seminário Seminário Estadual PIBID do Paraná: tecendo saberes / organizado por Dulcyene Maria Ribeiro e Catarina Costa Fernandes — Foz do Iguaçu: Unioeste; Unila, 2014Este trabalho relata uma aula desenvolvida pelas alunas do Curso de Formação de Docentes do Instituto Estadual de Educação de Londrina com a colaboração dos Bolsistas do Programa Institucional de Bolsas de Iniciação à Docência – PIBID – Subprojeto de Matemática, para alunos de primeiro ano do Ensino Fundamental utilizando o teatro como forma de apresentar conteúdos matemáticos como números, sequência de números, operações básicas como adição, subtração e conteúdos de língua portuguesa como leitura e escrita de número

Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model

BACKGROUND: Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide, water-soluble vitamin B3, may play a key role in cancer prevention through its activities in cellular repair. However, to date, evidence towards identifying the genetic alterations of nicotinamide in cancer prevention has not been provided. Here, we search for the molecular signatures of cancer prevention by nicotinamide using a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urinary bladder cancer model in mice. METHODOLOGY/PRINCIPAL FINDINGS: Via microarray gene expression profiling of 20 mice and 233 human bladder samples, we performed various statistical analyses and immunohistochemical staining for validation. The expression patterns of 893 genes associated with nicotinamide activity in cancer prevention were identified by microarray data analysis. Gene network analyses of these 893 genes revealed that the Myc and its associated genes may be the most important regulator of bladder cancer prevention, and the gene expression signature correlated well with protein expression data. Comparison of gene expression between human and mouse revealed that BBN-induced mouse bladder cancers exhibited gene expression profiles that were more similar to those of invasive human bladder cancers than to those of non-invasive human bladder cancers. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that nicotinamide plays an important role as a chemo-preventive and therapeutic agent in bladder cancer through the regulation of the Myc oncogenic signature. Nicotinamide may represent a promising therapeutic modality in patients with muscle-invasive bladder cancer