Low Expression of E-Cadherin and Cdh1 Variants Associated with Diffuse Gastric Cancer

ABSTRACT Background Reduced or null expression of E-cadherin protein is a frequent cause of diffuse gastric cancer (DGC). More than 50% of patients with DGC present somatic variants in CDH1 gene. Objectives The objectives of this study were to study E-cadherin expression and identify variants in the CDH1 gene in gastric tumors of patients with DGC. Methods We studied 18 Mexican DGC patients who attended a hospital of the Mexican Social Security Institute; E-cadherin expression was determined by immunohistochemistry, and variants were identified by Sanger sequencing in promoter and coding regions. Predictive analysis was performed using PolyPhen-2 and HOPE software. Results We found that 56% of DGC patients showed reduced expression of E-cadherin. All patients carried CDH1 variants; overall, 12 different CDH1 variants were identified. Predictive analysis revealed that the rs114265540 variant was probably damaging, with a value of 0.985, indicating a functional impact on the E-cadherin protein. Variants rs34939176 and rs33964119 were identified as risk factors for DGC (odds' ratios [OR] = 31.3, 95% CI 6.3-154.0, p < 0.001; OR = 6.1, 95% CI 2.0-19.0, p < 0.001, respectively) given their elevated frequency and by comparing it with those reported for MXL population in the 1000 Genomes Project database. Conclusions In this Mexican population, the percentage of diffuse gastric tumors with reduced expression of E-cadherin was similar to that reported in other populations. All gastric tumors of DGC patients studied had somatic CDH1 gene variants; however, the rs114265540, rs34939176, and rs33964119 variants were importantly related to DGC.

Low expression of E-Cadherin and CDH1 variants associated with diffuse gastric cancer.

Background: Reduced or null expression of E-cadherin protein is a frequent cause of diffuse gastric cancer (DGC). More than 50% of patients with DGC present somatic variants in CDH1 gene. Objectives: The objectives of this study were to study E-cadherin expression and identify variants in the CDH1 gene in gastric tumors of patients with DGC. Methods: We studied 18 Mexican DGC patients who attended a hospital of the Mexican Social Security Institute; E-cadherin expression was determined by immunohistochemistry, and variants were identified by Sanger sequencing in promoter and coding regions. Predictive analysis was performed using PolyPhen-2 and HOPE software. Results: We found that 56% of DGC patients showed reduced expression of E-cadherin. All patients carried CDH1 variants; overall, 12 different CDH1 variants were identified. Predictive analysis revealed that the rs114265540 variant was probably damaging, with a value of 0.985, indicating a functional impact on the E-cadherin protein. Variants rs34939176 and rs33964119 were identified as risk factors for DGC (odds' ratios [OR] = 31.3, 95% CI 6.3-154.0, p < 0.001; OR = 6.1, 95% CI 2.0-19.0, p < 0.001, respectively) given their elevated frequency and by comparing it with those reported for MXL population in the 1000 Genomes Project database. Conclusions: In this Mexican population, the percentage of diffuse gastric tumors with reduced expression of E-cadherin was similar to that reported in other populations. All gastric tumors of DGC patients studied had somatic CDH1 gene variants; however, the rs114265540, rs34939176, and rs33964119 variants were importantly related to DGC.

Lieber-DeCarli Diet Promotes Different Hepatic Histological Changes During Early and Late Pregnancy: An Example of Maternal Resilience.

BACKGROUND/AIM: During pregnancy, maternal liver can be affected by ethanol (ETOH) intake, whose effects depend on concentration levels ingested. This study aims to describe histological and serum marker characteristics of maternal liver during two metabolic conditions: gestation (G), and sustained ETOH intake, in early and late pregnancy. MATERIALS AND METHODS: Wistar rats were fed with Lieber-DeCarli diet during pregnancy, following an experimental protocol that allows a semi-chronic intake of ETOH (5%). Liver and serum samples were processed for histological characterization and biochemical profiling. Hematoxylin/eosin and Schiff's Periodic Acid staining were used. RESULTS: During pregnancy, a significant elevation in ballooned and edamatous hepatocytes, and a significant increase in micro and macrovesicular deposits were observed in rats fed with the ETOH diet at gestation days 3G, 8G and 15G. These changes were reverted by 20G. Liver glycogen content increased significantly at 15G. Serum metabolites in pregnant rats fed with the ETOH diet showed a significant reduction in urea (from 3G to 15G), an increase in albumin and uric acid at 20G, and a reduction in creatinine. Number of offsprings and weight of male newborns were reduced by 20% and 14%, respectively. Liver function markers in serum showed no significant changes. CONCLUSION: ETOH diet intake promotes hepatic histological changes and histological modifications during pregnancy. These results support the assumption that pregnancy is an adaptive procedure that is associated with nutritional conditions and has a strong influence on hepatic histology. They suggest that pregnancy promotes a state of resilience to the liver function during the sustained intake of 5% ETOH.

Characterization of Nuclear Pleomorphism and Tubules in Histopathological Images of Breast Cancer.

Breast cancer (BC) diagnosis is made by a pathologist who analyzes a portion of the breast tissue under the microscope and performs a histological evaluation. This evaluation aims to determine the grade of cellular differentiation and the aggressiveness of the tumor by the Nottingham Grade Classification System (NGS). Nowadays, digital pathology is an innovative tool for pathologists in diagnosis and acquiring new learning. However, a recurring problem in health services is the excessive workload in all medical services. For this reason, it is required to develop computational tools that assist histological evaluation. This work proposes a methodology for the quantitative analysis of BC tissue that follows NGS. The proposed methodology is based on digital image processing techniques through which the BC tissue can be characterized automatically. Moreover, the proposed nuclei characterization was helpful for grade differentiation in carcinoma images of the BC tissue reaching an 0.84 accuracy. In addition, a metric was proposed to assess the likelihood of a structure in the tissue corresponding to a tubule by considering spatial and geometrical characteristics between lumina and its surrounding nuclei, reaching an accuracy of 0.83. Tests were performed from different databases and under various magnification and staining contrast conditions, showing that the methodology is reliable for histological breast tissue analysis.

Rectus abdominis muscle thickness as a predictor of peritoneal catheter dysfunction in emergency-start peritoneal dialysis patients.

BACKGROUND: Percutaneous insertion of a peritoneal dialysis catheter (PDc) is an alternative to open surgical techniques, and the anatomical characteristics of the abdominal wall may predict PDc dysfunction. We evaluated the role of rectus abdominis muscle (RAM) thickness as a predictor of PDc dysfunction. MATERIALS AND METHODS: A prospective cohort of emergency-start PD patients (EmPD) who had their first percutaneous PDc insertion were included. PDc failure was defined as the removal of a PDc due to mechanical failure within the first 30 PD fluid exchanges. Clinical variables were recorded. The skin to parietal peritoneum depth and RAM thickness were determined by abdominal ultrasound. Univariate and multivariate logistic regression models were developed to test associations between clinical parameters and PDc dysfunction. RESULTS: Over 6 months, 119 patients underwent PDc insertion; 73 (61.3%) were males, with a mean age of 46.0 ± 17.8 years. The mean skin-to-peritoneum depth was 2.5 ± 1.0 cm, the RAM thickness was 0.91 ± 0.3 cm, and catheter implantation was successful in 116 (97.4%) patients. Insertion failed in 3 (2.5%) cases, and 30 (25.8%) patients presented with catheter dysfunction. Univariate analysis indicated that RAM thickness ≥ 1.0 cm, skin-to-peritoneum depth > 2.88 cm, abdominal waist > 92.5 cm, and skin-to-RAM fascia distance > 2.3 cm were associated with PDc dysfunction; in multivariate logistic regression analysis, only greater RAM thickness remained a significant predictor (OR 1.6, 95% CI 1.38 - 1.88, p < 0.001). CONCLUSION: In EmPD patients, RAM thickness is associated with PDc dysfunction and could aid in identifying patients at risk for PDc dysfunction in emergency settings. Additional adequately powered studies are needed to confirm our findings.

Changes in amino acid profiles and liver alterations in pregnant rats with a high carbohydrate/low protein diet.

INTRODUCTION AND AIM: Intake of a high-carbohydrate, low-protein diet (HCD/LPD) during pregnancy promotes metabolic disturbances. It has been suggested that liver function during pregnancy contributes to the synthesis of proteins necessary for fetal development during this stage. The liver is a site of response to the synthesis of macronutrients such as proteins. However, it is unknown how HCD/LPD is associated with modifications to the amino acid profiles and hepatic alterations in the maternal environment during pregnancy. MATERIALS AND METHODS: A transverse longitudinal study was done in primiparous mothers during gestation (G) (G1 day 1, G5 day 5, G15 day 15, and G20 day 20). Histological analysis was used to assess hepatic alterations, and amino acid profiles in the liver were analyzed with high performance liquid chromatography (HPLC). Food and water intake was quantified, and peripheral biochemical indicators in serum were measured. RESULTS: Mothers with HCD/LPD had increased micro and macro vesicles of fat, necrosis, and inflammation in the liver on G5. The total concentration of hepatic amino acids increased by 40% on G1, 17% on G5, and 25% on G15; and, there was a 12% decrease on G20. The following increases were observed in the liver on G1: arginine 68%, histidine 75%, alanine 18%, methionine 71%, and phenylalanine 51% (p>0.05); on G5: arginine 12%, methionine 34%, and phenylalanine 83% (p>0.05); on G15: arginine and phenylalanine 66%, tryptophan 81% and histidine 60.4% (p>0.05); and on G20: arginine 32% (p>0.05). No weight loss, changes in food consumption, or hepatomegaly occurred. CONCLUSIONS: HCD/LPD during pregnancy in primiparous mothers may promote development of fat vesicles. Possibly, this condition causes metabolic adaptations and nitrogen management reflected in decreased levels of serum urea and altered amino acid profiles in the liver.

Dietary fat and antioxidant vitamin intake in patients of neurodegenerative disease in a rural region of Jalisco, Mexico.

OBJECTIVE: To evaluate and compare the intake of lipids and (A, E, and C) vitamins in patients with and without possible neurodegenerative diseases. METHODS: Twenty adults with possible Alzheimer's disease or Parkinson's disease and 41 control subjects (50-89 years old) from a rural region were studied. Dietary intake was evaluated with the analysis of macronutrients and micronutrients conducted by a food frequency questionnaire and 24 hours dietary record. Analyses were adjusted for age, sex, body mass index, and energy intake. Through interrogation and use of medical record form of health secretary we obtained information about the sociodemographic characteristics. Multivariate analysis of variance to allow for covariated adjustment was used. RESULTS: Patients had a lower energy intake, vitamin C (P = 0.016), fruits (P < 0.001), vegetables (P = 0.037), and oils and fat (P = 0.002), than the controls. Interestingly, the C vitamin intake in patients was still higher than the recommended. Patients had a higher consumption of cereals (P = 0.017), high-animal fat diet (P = 0.024), and whole milk (P < 0.001); 2.4% of the controls smoke and 5% are alcohol consumers. Eighty-five percent of patients and 78% of the controls do not have physical activity. Family history of subjects in this study indicated chronic diseases. CONCLUSION: The subjects included in this study had a high intake of C vitamin, this is due to the consumption of fruits and vegetables. However, patients with possible Alzheimer's or Parkinson's disease had a lower intake of fruits and vegetables, which could be due to type of food to which they have access.

Oxidative stress is increased in serum from Mexican patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. METHODS: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. RESULTS: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress.