PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients.

PML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. Seventy-four metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine-based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. PML down-regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients with PML down-regulation than in patients with preserved PML expression (60%) (P = 0.006). Median TTP was 5.5 months when PML was down-regulated versus 11.9 months in case of preserved PML expression (P < 0.0001). A statistical significant difference was also detected in OS (15.6 and 24.5 months, respectively, P = 0.003). The impact of PML down-regulation on TTP and OS was statistically significant also in a multivariate model. This study represents the first evidence of a possible correlation between PML protein expression and outcome of metastatic colorectal cancer patients treated with oxaliplatin/fluoropyrimidine-based first line therapy.

Screening E-cadherin germline mutations in Italian patients with familial diffuse gastric cancer: an analysis in the District of Urbino, Region Marche, Central Italy.

AIMS & BACKGROUND: Hereditary diffuse gastric cancer is a recently defined cancer syndrome caused by inactivating, heterozygous germline mutations in the E-cadherin gene (CDH1). To date, 16 truncating germline CDH1 mutations have been described in hereditary diffuse gastric cancer families in different ethnic groups, but so far, no investigation has been addressed to Italian patients. In the District of Urbino, Region Marche, Central Italy, gastric cancer is the most common tumor in men and it is the second in women after breast cancer. In this area, we investigated CDH1 mutations in patients who fulfilled the hereditary diffuse gastric cancer criteria. MATERIAL AND METHODS: Consecutive patients with diffuse gastric cancer were considered eligible for the study. After pedigree analysis, patients who met the International Gastric Cancer Linkage Consortium criteria were studied for CDH1 mutations. After blood samples collection and DNA extraction, standard polymerase chain reaction and sequencing techniques were used for CDH1 analysis. RESULTS: In a study population of 98 patients with diffuse gastric cancer, 11 patients (11%) showed familial clustering and 3 of them met the International Gastric Cancer Linkage Consortium criteria for hereditary diffuse gastric cancer. None of the 3 patients showed inactivating germline mutation in CDH1. CONCLUSIONS: According to recent studies, the frequency of CDH1 inactivating germline mutations in patients who fulfil the hereditary diffuse gastric cancer criteria may be lower than that reported in early investigations. The results of the present study in a population of Italian patients seem to confirm these data. It is likely that unidentified mutations in CDH1 or other involved genes contribute to diffuse gastric cancer susceptibility.

Utilidad de las proteínas de pollo y de soja en ratas nutridas o desnutridas con diarrea inducida por lactosa / Utility of chicken and soybean protein in well-nourished or undernourished rats with lactose-induced diarrhea

En el tratamiento nutricional de la diarrea infantil se han utilizado con éxito preparaciones líquidas que contienen pollo combinado con cereales y/o tubérculos, que se preparan en la institución de hospitalización o en la casa. En un estudio anterior, se comparó la efectividad de fórmulas con proteínas de pollo o aislado de soja en el tratamiento de la diarrea infantil. El objetivo de este trabajo fue estudiar en ratas con o sin diarrea, la utilización de las proteínas y la disponibilidad de nutrientes de dietas preparadas con pollo o aislado proteico de soja, para determinar si los resultados obtenidos en los niños eran comparables a los obtenidos en ratas. Dado que la diarrea y la desnutrición frecuentemente están presentes de manera simultánea, también se estudiaron grupos de animales con o sin diarrea previamente desnutridos. Los resultados mostraron que durante la diarrea las ratas desnutridas fueron igualmente eficientes que las nutridas en utilizar los nutrientes presentes en las dietas con pollo o soja, por lo que no experimentaron un deterioro nutricional mayor que las nutridas. Adicionalmente, la severidad de la diarrea fue similar en las ratas asignadas a las dietas con pollo o soja. Asimismo, las ratas con diarrea consumieron, crecieron, absorbieron y retuvieron menos de los macronutrientes dietarios que las ratas control. Sin embargo, este efecto de la diarrea fue similar en las ratas que consumieron proteína de soja o de pollo. Como estos resultados coinciden con los obtenidos previamente en niños con diarrea aguda, se concluye que la proteína de soja es tan efectiva como la de pollo en el manejo nutricional de la diarrea y que la diarrea producida con lactosa en ratas es un modelo apropiado para el estudio de las consecuencias nutricionales de la misma.

In the nutritional treatment of diarrhea, good results have been obtained using liquid formulas with chicken meat together with cereals and/or starchy vegetables, prepared at home or at the clinic. In a previous study, formulas prepared with chicken meat or isolated soybean protein were tested in the treatment of infantile diarrhea. In order to determine if the results obtained in children could be reproduced in rats, the objective of the present study was to evaluate the effectiveness of the same diets in the nutritional treatment of well-nourished as well as undernourished rats with lactose induced diarrhea. The results showed that all the rats with diarrhea absorbed and retained less of the dietary nutrients and consequently, grew less than their counterparts without diarrhea. However, the absorption and retention measured in the nourished as well as in the undernourished rats were similar, indicating that a short period of malnutrition previous to the diarrhea episode, did not affect rats' absorption capacity. In addition, similarly to the results previously obtained in children, the rats with lactose induced diarrhea utilised equally well the dietary nutrients present in the chicken as well as in the soybean protein based diets. These results confirmed the value of isolated soybean protein in the nutritional treatment of diarrhea and showed that lactose induced diarrhea in rats is an appropriate model to study the nutritional consequences of diarrhea.