Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Experimental model of induction of diabetes mellitus in rats Modelo experimental de indução do diabetes mellitus em ratos

Diabetes mellitus is a potentially morbid condition with high prevalence worldwide, thus being a major medical concern. Experimental models play an important role in understanding such a disease, which is treatable only. This study describes a rat diabetes mellitus model induced by administering a reduced dose of alloxan, thus greatly reducing the animals’ death rate.<br>O diabetes mellitus é uma condição mórbida da maior importância no contexto da medicina. Este artigo decreve um dos modelos de indução do diabetes mellitus com aloxano, uma das substâncias que provocam a hiperglicemia permanente em várias espécies. Com base na literatura, tem o intuito de estabelecer esse modelo como uma opção para investigar as complicações do diabetes mellitus e seus tratamentos. Tese, ainda, considerações sobre perspectivas de aplicações deste modelo, ainda pouco utilizado

Environmentally friendly system for the degradation of multipesticide residues in aqueous media by the fenton’s reaction

A Fenton oxidation system employing zero-valent iron (whose source was swarf, a residue of metallurgical industries, in powder form) and hydrogen peroxide for the treatment of an aqueous solution with six pesticides was developed, and the effect of the iron metal content, pH, and hydrogen peroxide concentration was evaluated. The characterization of the aqueous solution resulted in: pH 5.6, 105 mg L−1 of dissolved organic carbon, and 44.6 NTU turbidity. In addition, the characterization of the swarf by FAAS and ICP-MS showed 98.43±7.40 % of zero-valent iron. The removal was strongly affected by the content of iron metal, pH, and hydrogen peroxide concentration. The best degradation conditions were 2.0 g swarf, pH 2.0, and 5 mmol L−1 H2O2. At the end of the treatment, the pesticide degradation ranged from 60 to 100 %, leading to 55 % mineralization. Besides, all hydrogen peroxide was consumed and the determination of total dissolved iron resulted in2mgL−1. Thus, the advantages of this system are rapid degradation (up to 20 min), high-degradation rates, simple handling, and low cost