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.

Mediation of a glutamate antagonist, a NOS inhibitor and antioxidants with - SH groups on striatal dopamine release induced by clothianidin

Is Clothianidin is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine if the administration of a glutamate antagonist (APV), a NOS inhibitor (L-NAME) or two antioxidants (glutathione, and dithiothreitol,) prevent the increase in the striatal dopamine levels induced by clothianidin, using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of clothianidin (3.5 mM) produced an increase in striatal dopamine levels of 2462 ± 627%, with respect to basal levels. Coadministration of 0.65 mM APV and 3.5 mM clothianidin generated an increase in extracellular dopamine levels of 1089 ± 243.5%, being this increase 55.7% lower than the generated by clothianidin alone. Coadministration of 0.1 mM L-NAME and 3.5 mM clothianidin generated a significant increase in extracellular dopamine levels of 836.5 ± 150.6%., this increase is 70% lower than the generated by clothianidin alone. Coadministration of 3.5 mM clothianidin in combination with 0.4 mM glutathione induced an increase in striatal dopamine levels of 465.6 ± 126.8% , indicating that the administration of glutathione results in an inhibition of 81% of the effect generated by the infusion of clothianidin alone. Administration of 3.5 mM clothianidin associated with 0.005 mM dithiothreitol induced an increase in extracellular dopamine levels in the striatum of 693.8 ± 117.8% with respect to basal levels, being this increase 72% lower that the generated by clothianidin alone. Our results suggest that the effect of clothianidin on striatal dopamine release can be reduced by the administration of a glutamate antagonist, a NOS inhibitor or antioxidants with –SH groups, which suppose a simple protection mechanism against the damage caused for clothianidin (AU)

La clotianidina es un insecticida neonicotinoide con actividad selectiva sobre los receptores de acetilcolina. El objetivo de este estudio es comprobar si un inhibidor de los receptores glutamatérgicvos (APV), un inhibidor de la óxido nítrico sintetasa (L-NAME) y dos antioxidantes como el glutatión y el dithiotreitol previene la liberación de dopamina inducida por la clotianidina, usando la técnica de microdiálisis en ratas conscientes y en libre movimiento. La administración intraestriatal de clothianidina (3.5 mM) produce un aumento de 2462 ± 627%, de los niveles estriatales de dopamina respecto a los niveles basales. La coadministracion de 0.65 mM de APV y 3.5 mM d clothianidina genera un a aumento de 1089 ± 243.5% de los niveles estriatales de dopamina, siendo este incremento 55.7% más bajo que el generado por la clotianidina sola. La Coadministration de.0,1 mM de L-NAMEy3.5 mM de clotianidina genera un aumento de 836.5 ± 150.6% de los nivelesextracelulares de dopamina, siendo este aumento un 55.7% más bajo que el generado por la clotianidina sola. La coadministracion of 3.5 mM clothianidina en combinación con 0.4 mM de glutatión induce un aumento de 465.6 ± 126.8% de los niveles estriatales de dopamina, indicando que la administración de glutatión provoca una inhibición del 81% del efecto generado por la infusión de clotianidina sola. La administración de 3.5 mM de clothianidinajunto con 0.005 mM de diithiothreitol induce un aumento de 693.8 ± 117.8% en los niveles extracelulares de dopamina en el estriado, siendo este incremento 72% más bajo que el generado por la clotianidina sola. Nuestros resultados sugieren que el efecto de la clotianidina sobre la liberación estriatal de dopamina pueden ser reducidos por la administración de un antagonista glutamatérgico, un ihibibidor de la NOS o por antioxidantes con grupo –SH, lo cualsupone un simple mecanismo de protección contra el daño causadopor la clotianidina (AU)

[Hystopathology of gastric cancer] / Histopatologia do câncer de estômago (classificação de Lauren) em amostra de pacientes hospitalares no Rio de Janeiro, 1980-1995.

This study draws a random sample (334 individuals) of all patients diagnosed with stomach cancer from 1980 to 1995 at the National Cancer Institute in Rio de Janeiro, Brazil, and reviews histopathological data. Agreement between previous and present classification of the histopathological material (Laurén's classification) was considered quite substantial (kappa = 0.65). Based on this classification, a statistically nonsignificant trend towards decline in the intestinal type of stomach cancer among older individuals (60 years old or older) from both genders was observed (males: 41.0% in 1980-1985, 37.9% in 1986-1990, and 28.8% in 1991-1995; females: 41.4%, 31.5%, and 15.2%, respectively). Proportions of the intestinal type among younger patients from both genders remained stable throughout the period.