The potential of mRNA expression evaluation in predicting HER2 positivity in gastroesophageal cancer

Gastroesophageal cancer (GEC) is an aggressive disease characterized by a high frequency of metastasis and poor overall survival rates. GEC presents HER2 overexpression in 5 to 25% of tumors eligible for HER2-targeted therapy. HER2 evaluation requires protein levels and copy number alteration analyses by immunohistochemistry (IHC) and in situ hybridization (FISH or SISH), respectively. These are semiquantitative methodologies that need an expert and well-trained pathologist. Therefore, the use of new surrogate methods for HER2 evaluation in cancer, such as gene expression analysis, might improve GEC HER2 classification. We evaluated HER2 positivity in GEC through conventional IHC and SISH analyses and investigated the potential application of HER2 mRNA expression by quantitative PCR to categorize GEC samples as HER2-positive or HER2-negative. Among 270 GEC samples, 10.9% were HER2-positive by IHC and SISH analyses. HER2 mRNA was overexpressed in HER2-positive GEC samples and presented high accuracy in distinguishing those tumors from HER2-negative GEC. Nevertheless, HER2 mRNA analysis was not capable of classifying HER2-equivocal GEC samples into HER2-positive or -negative according to SISH data. Quantitative PCR analysis showed HER2 overexpression in HER2-positive GEC samples. Nevertheless, HER2 mRNA analysis failed to classify HER2-equivocal GEC according to SISH data.

Maternal protein restriction during lactation modulated the expression and activity of rat offspring hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1 during development

Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring’s CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8– fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities’ alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development.

Determinação da atividade antioxidante In vitro das bebidas de café e chás verde e preto / Determination of In vitro antioxidant activity of the beverages of coffee, green tea and black tea

Conforme demonstrado em diversos estudos, determinadas plantas e alimentos, apresentam propriedades protetoras à saúde devido à presença de antioxidantes. Sendo assim, o presente trabalho teve como objetivo comparar o efeito antioxidante in vitro de bebidas comercializadas de café, chá verde e chá preto, utilizando a combinação de diferentes metodologias. As bebidas foram preparadas no momento de uso, de acordo com as especificações do fabricante. Foram realizados testes para determinar o teor de polifenóis nas bebidas, e avaliar o seu poder redutor, bem como sua capacidade de quelar íons de metais de transição (Fe2+) sequestrar radicais livres, e inibir a peroxidação de lipídeos. O café apresentou maior teor de compostos fenólicos, seguido do chá verde e do chá preto (p<0,05). A análise dos resultados não revelou diferenças entre as três bebidas analisadas em relação ao poder redutor e à capacidade de inibir a peroxidação de lipídeos (p>0,05). A bebida de café apresentou uma maior atividade quelante do que o chá preto enquanto que o chá preto e o café apresentaram maior capacidade sequestrante de radicais DPPH em comparação com o chá verde. Os dados obtidos permitem sugerir que a bebida de café, provavelmente por ter maior concentração de polifenóis, pode ser considerada a melhor no que diz respeito à atividade antioxidante. Assim, a bebida de café, além de ser uma das bebidas mais populares do mundo por seu aroma e sabor, poderia também contribuir para a prevenção de danos oxidativos de maneira mais eficiente que os chás analisados neste estudo.(AU)

Numerous studies have demonstrated that certain plants and foods exhibit health protective properties due to the presence of antioxidants. In this sense, the present study aimed to compare the in vitro antioxidant effect of the commercialized beverages of coffee, green tea and black tea by using a combination of different methodologies. The beverages were prepared at the time of use, according to the manufacturer?s specifications. We determined the polyphenol content in the beverages and examined their reducing power, as well as their ability to chelate transition metal ions (Fe2+), scavenge free radicals, and inhibit lipid peroxidation. The beverage of coffee contained the highest amounts of phenolic compounds, being followed by green tea and black tea (p<0.05). The results revealed no differences among the three beverages regarding their reducing power and lipid peroxidation-inhibiting activity (p>0.05). The beverage of coffee displayed higher metal chelating ability than black tea. The beverages of black tea and coffee scavenged DPPH radical more effectively than green tea. The data obtained suggest that the beverage of coffee can be considered the best one regarding the antioxidant activity, probably due to its highest content of polyphenols. Thus, the beverage of coffee, one of the most popular beverages in the world for its aroma and flavor, could also contribute to prevent the oxidative damage more efficiently than the teas analyzed in this study.(AU)

Manifestaciones cutáneas de amiloidosis sistémica en tres pacientes / Cutaneous manifestations in three patients with systemic amyloidosis / Manifestações cutâneas de amiloidosis sistémica em três pacientes

La Amiloidosis Sistémica (AS) es un grupo heterogéneo de enfermedades caracterizadas por el depósito de proteínas fibrilares en los tejidos. Se presentan tres casos con compromiso cutáneo. Se revisan las amiloidosis sistémicas y se enfatiza en las características clínicas, especialmente las manifestaciones cutáneas, que son muy floridas en los pacientes reportados y consideradas clave para el diagnóstico temprano y el impacto en el pronóstico de esta patología.

Systemic amyloidosis is a group of heterogeneous diseases caused by tissue deposition of misfolded proteins. We report 3 cases of patients with systemic amyloidosis. Diagnosis in all cases was confirmed by biopsy. Here, we also briefly review the pathogenesis, diagnosis, treatment, and clinical manifestations, with a particular focus on cutaneous manifestations. Since such lesions appear early in the disease, we consider that accurately identifying them can have an impact on the prognosis of this affection.

A Amiloidosis Sistémica (AS) é um grupo heterogêneo de doenças caracterizadas pelo depósito de proteínas fibrilares nos tecidos. Apresentam-se três casos com compromisso cutâneo. Revisam-se as amiloidose sistémicas e se enfatiza nas características clínicas, especialmente as manifestações cutâneas, que são muito floridas nos pacientes reportados e consideradas clave para o diagnóstico precose e o impacto no prognóstico desta patologia.