Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer.

Gallbladder cancer is an aggressive disease with late diagnosis and no efficacious treatment. The Hippo-Yes-associated protein 1 (YAP1) signaling pathway has emerged as a target for the development of new therapeutic interventions in cancers. However, the role of the Hippo-targeted therapy has not been addressed in advanced gallbladder cancer (GBC). This study aimed to evaluate the expression of the major Hippo pathway components mammalian Ste20-like protein kinase 1 (MST1), YAP1 and transcriptional coactivator with PDZ-binding motif (TAZ) and examined the effects of Verteporfin (VP), a small molecular inhibitor of YAP1-TEA domain transcription factor (TEAD) protein interaction, in metastatic GBC cell lines and patient-derived organoids (PDOs). Immunohistochemical analysis revealed that advanced GBC patients had high nuclear expression of YAP1. High nuclear expression of YAP1 was associated with poor survival in GBC patients with subserosal invasion (pT2). Additionally, advanced GBC cases showed reduced expression of MST1 compared to chronic cholecystitis. Both VP treatment and YAP1 siRNA inhibited the migration ability in GBC cell lines. Interestingly, gemcitabine resistant PDOs with high nuclear expression of YAP1 were sensitive to VP treatment. Taken together, our results suggest that key components of the Hippo-YAP1 signaling pathway are dysregulated in advanced gallbladder cancer and reveal that the inhibition YAP1 may be a candidate for targeted therapy.

Can Histological Grade and Mitotic Index Replace Ki67 to Determine Luminal Breast Cancer Subtypes?

Introduction: Breast cancer can be classified into subtypes based on immunohistochemical markers, with Ki67 expression levels being used to divide luminal BC tumors in luminal A and B subtypes; however, Ki67 is not routinely determined due to a lack of standardization. Objective: To evaluate histological grade and Eliminate: the mitotic index to determine if they can be used as an alternative method to Ki67 staining for luminal subtype definition. Methods: We evaluated estrogen receptor positive breast cancer tissue samples. Pathological analysis included determination of Ki67. A low level of Ki67 was defined as <14% positive cells. Results: We evaluated 151 breast cancer samples; 24 (15,9%) were classified as I; 74 as HG II (49%), and 53 (35,1%) as HG III. The median value for Ki67 was 13% (range: <1% - 82%) and for MI was 2 (0-12). Histological grade I tumors exhibited Ki67 values significantly lower than HG II and III tumors (Anova, Tamhane test p=0,001). A higher Ki67 value was related to a higher MI (Rho Sperman p=0,336; R2= 0,0273). ROC curve analysis determined that a MI ≥ 3 had a sensibility of 61.9% and specificity of 66.7% in predicting a high Ki67 value (≥14%) (area under the curve: 0,691; p =0,0001). A HG I tumor or HG II-III with MI ≤2, had a high probability of corresponding to a LA tumor (76,3%), as defined using Ki67 expression, while the probability of a LB subtype was higher with HG II-III and a MI ≥3 (57.4%). Global discrimination was 68.1%. Conclusions: For the LA subtype, our predictive model showed a good correlation of HG and MI with the classification based on Ki67<14%. In the LB subtype, the model showed a weak correlation; therefore Ki67 determination seems to be needed for this group of patients.

Consumo de alimentos ultraprocesados y su asociación con el exceso de peso y la obesidad abdominal en jóvenes que inician la educación superior / Ultra-processed food consumption and its association with overweight and abdominal obesity in young people who begin higher education

Fundamentos: En la etapa universitaria muchos jóvenes aumentan el consumo de alimentos ultraprocesados(AUP). El objetivo fue analizar la asociación entre el consumo de AUP con el exceso de peso y la obesidadabdominal en jóvenes que inician la educación superior.Métodos: Estudio transversal analítico. Participaron 139 jóvenes que ingresaron a la Facultad de Ciencias dela Salud de una universidad de Valparaíso, Chile. El consumo alimentario se evaluó mediante una Encuesta deTendencia de Consumo Cuantificada, se utilizó el sistema NOVA para clasificar 26 AUP en 8 subgrupos. Semidió el peso, estatura y perímetro de cintura para determinar el Índice de Masa Corporal y el diagnóstico deobesidad abdominal.Resultados: Los jóvenes con exceso de peso consumían con mayor frecuencia margarina, salsas y grasas parauntar (p=0,007), embutidos y otros productos cárnicos reconstituidos (p=0,049) y de comida rápida (p=0,003);y aquellos con obesidad abdominal consumían con mayor frecuencia productos de pastelería, galletas ychocolates (p=0,037), margarina, salsas y grasas para untar (p=0,001) y de comida rápida (p<0,000).Conclusiones: Algunos subgrupos de AUP se asociaron con exceso de peso y obesidad abdominal. Disminuirel consumo de AUP podría mejorar el estado nutricional de los jóvenes. (AU)

Background: in the university stage many young people increase the consumption of ultra-processed food(UPF). The aim was to analyze the association between the consumption of UPF, overweight and abdominalobesity in young people who begin higher education.Methods: Analytical cross-sectional study. 139 young people participated who entered to the Faculty ofHealth Sciences of a university in Valparaíso, Chile. Food consumption was assessed using a QuantifiedConsumption Trend Survey; the NOVA system was used to classify 26 UPF into 8 subgroups. Body weight,height and waist circumference were measured to determine the Body Mass Index and the diagnosis ofabdominal obesity.Results: Young people with overweight more frequently consumed margarine, sauces and spreadable fats(p=0,007), sausages and other reconstituted meat products (p=0,049), and fast food (p=0,003); and thosewith abdominal obesity more frequently consumed pastry products, cookies and chocolates (p = 0,037),margarine, sauces and spreadable fats (p = 0,001) and fast food (p <0,000).Conclusions: Some UPF subgroups were associated with overweight and abdominal obesity. Decrease theconsumption of UPF could improve the nutritional status of young people. (AU)

Consumo alimentario y cumplimiento de recomendaciones dietéticas en estudiantes que ingresan a la universidad / Food consumption and adherence to dietary recommendations for students entering university

INTRODUCCIÓN: Los jóvenes se consideran una población sana, sin embargo, los malos hábitos alimentarios podrían contribuir al aumento de enfermedades cardiometabólicas, discapacidad y muerte prematura. OBJETIVO: Identificar el consumo alimentario y cumplimiento de las recomendaciones dietéticas en estudiantes que ingresaron a una universidad estatal. MATERIALES Y MÉTODOS: Estudio de tipo descriptivo con diseño transversal en el que participaron estudiantes entre 17 y 24 años, que ingresaron a la Facultad de Ciencias de la Salud de una universidad estatal, quienes respondieron una encuesta de Tendencia de Consumo Cuantificado semanal auto administrada que consultó sobre el consumo de 89 alimentos y preparaciones. Para la evaluación antropométrica se midió el peso, la estatura y la circunferencia de cintura. Los datos fueron procesados con el programa SPSS V. 24. RESULTADOS: Participaron 139 jóvenes de 18.7 ± 1.1 años, 29.5% con exceso de peso. El consumo fue bajo en frutas y verduras, lácteos, legumbres, pescados y frutos secos, y alto en cereales blancos, carnes procesadas, comida chatarra, jugos, bebidas y alimentos azucarados. Sobre el 40% reportó un consumo excesivo de energía y macronutrientes, ácidos grasos saturados, vitaminas A, B1, B2, B3, B6, fósforo, hierro, sodio y yodo, mientras que el 30% presentó una ingesta deficiente en ácidos grasos poliinsaturados omega-3, omega-6, vitaminas B9 y C, calcio, potasio y fibra dietética. DISCUSIÓN: Investigaciones reportan que la alimentación de los estudiantes universitarios es poco variada y desequilibrada, excedida en proteínas y deficiente de calcio, hierro, vitamina A, ácidos grasos poliinsaturados omega-3, y fibra dietética. CONCLUSIONES: A pesar de la buena o excesiva ingesta en energía y macronutrientes, existe deficiencia en el consumo de ácidos grasos poliinsaturados, ciertas vitaminas, minerales y fibra dietética, y exceso en el consumo de nutrientes críticos, evidenciando la mala calidad de la dieta

INTRODUCTION: Young people are considered to be a healthy population; however, poor eating habits may contribute to increased cardiometabolic diseases, disability and premature death. Objetive. Identify food consumption and compliance with dietary recommendations in students who entered a state university. MATERIALS AND METHODS: A cross-sectional descriptive study involving 17-24-year-old students, who entered the Faculty of Health Sciences of a state university, who answered a self-administered weekly quantified consumption trend survey consulted on the consumption of 89 foods and preparations. For the anthropometric evaluation, weight, height and waist circumference were measured. The data were processed with the SPSS V. 24. RESULTS: 139 youths participated in 18.7 ± 1.1 years, 29.5% were overweight. Consumption was low in fruits and vegetables, dairy products, legumes, fish and nuts, and high in white cereals, processed meats, junk food, juices, beverages and sugary foods. Over 40% reported excessive intake of energy and macronutrients, saturated fatty acids, vitamins A, B1, B2, B3, B6, phosphorus, iron, sodium and iodine, while 30% had a deficient intake of polyunsaturated fatty acids Omega -3, Omega-6, vitamins B9 and C, calcium, potassium and dietary fiber. DISCUSSION: Research reports that college students are unhealthy and unbalanced, over-protein and deficient in calcium, iron, vitamin A, Omega-3 polyunsaturated fatty acids, and dietary fiber. CONCLUSIONS: In spite of good or excessive intake of energy and macronutrients, there is a deficiency in the consumption of polyunsaturated fatty acids, certain vitamins, minerals and dietary fiber, and excessive consumption of critical nutrients, evidencing the poor quality of the diet