A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma

Background

The TNM Classification of Malignant Tumours (TNM) staging system is the primary means of determining a prognosis for gastric adenocarcinoma (GC). However, tumor behavior in the individual patient is unpredictable and in spite of treatment advances, a classification of 'advanced stage' still portends a poor prognosis. Thus, further insights from molecular analyses are needed for better prognostic stratification and determination of new therapeutic targets.

Methods

A total of fifty-one fresh frozen tumor samples from patients with histopathologically confirmed diagnoses of GC, submitted to surgery with curative intent, were included in the study. Total RNA was extracted from an initial group of fifteen samples matched for known prognostic factors, categorized into two subgroups, according to patient overall survival: poor (<24 months) or favorable (at or above 24 months), and hybridized to Affymetrix Genechip human genome U133 plus 2.0 for genes associated with prognosis selection. Thirteen genes were selected for qPCR validation using those initial fifteen samples plus additional thirty-six samples.

Results

A total of 108 genes were associated with poor prognosis, independent of tumor staging. Using systems biology, we suggest that this panel reflects the dampening of immune/inflammatory response in the tumor microenvironment level and a shift to Th2/M2 activity. A gene trio (OLR1, CXCL11 and ADAMDEC1) was identified as an independent marker of prognosis, being the last two markers validated in an independent patient cohort.

Conclusions

We determined a panel of three genes with prognostic value in gastric cancer, which should be further investigated. A gene expression profile suggestive of a dysfunctional inflammatory response was associated with unfavorable prognosis.     

Sociodemographic,sexual, and reproductive variables associated with pregnancy among adolescents from low socioeconomic background

Adolescent pregnancy remains a public health concern in both developed and developing countries. Portugal and Brazil represent some of the best examples of this phenomenon. The present study aimed to identify sociodemographic, sexual, and reproductive health-related variables associated with adolescent pregnancy among students from low socioeconomic backgrounds in both countries. The sample included 984 female adolescents, among whom 215 became pregnant. Living with a partner and lack of information about sex and contraception from the family were the best explicative factors for pregnancy occurrence in both countries. Country-specific variables were also identified. Our results may contribute to developing global preventive interventions, addressing the school as an ideal setting for primary intervention and considering culture-specific characteristics of high-risk populations.     

Platelet‐Rich Plasma,Low‐Level Laser Therapy,or Their Combination Promotes Periodontal Regeneration in Fenestration Defects: A Preliminary In Vivo Study

Background: This study histomorphometrically analyzes the influence of platelet‐rich plasma (PRP), low‐level laser therapy (LLLT), or their combination on the healing of periodontal fenestration defects (PFDs) in rats. Methods: PFDs were surgically created in the mandibles of 80 rats. The animals were randomly divided into four groups: 1) C (control) and 2) PRP, defects were filled with blood clot or PRP, respectively; 3) LLLT and 4) PRP/LLLT, defects received laser irradiation, were filled with blood clot or PRP, respectively, and then irradiated again. Animals were euthanized at either 10 or 30 days post‐surgery. Percentage of new bone (NB), density of newly formed bone (DNB), new cementum (NC), and extension of remaining defect (ERD) were histomorphometrically evaluated. Data were statistically analyzed (analysis of variance; Tukey test, P <0.05). Results: At 10 days, group PRP presented ERD significantly lower than group C. At 30 days, group PRP presented NB and DNB significantly greater than group C. Groups LLLT, PRP, and PRP/LLLT showed significant NC formation at 30 days, with collagen fibers inserted obliquely or perpendicularly to the root surface. NC formation was not observed in any group C specimen. Conclusions: LLLT, PRP, or their combination all promoted NC formation with a functional periodontal ligament. The combination PRP/LLLT did not show additional positive effects compared to the use of either therapy alone.     

Distribution of Mast Cells and Macrophages and Expression of Interleukin-6 in Periapical Cysts

Introduction

Mast cells and macrophages are important components of the inflammatory infiltrate found in inflammatory periapical diseases. Several cytokines participate in the mechanisms of inflammation, tissue repair, and bone resorption associated with periapical cysts. The aim of the present study was to evaluate the distribution of mast cells and macrophages and the expression of interleukin-6 (IL-6) in periapical cysts.

Methods

Thirty periapical cysts were selected for the study, and clinical, demographic, and gross information from the cases was obtained from the laboratory records. Five-micrometer sections stained with hematoxylin-eosin were reviewed for analysis of the microscopic features of the cysts, and 3-μm sections on silanized slides were used for immunohistochemical reactions with anti-tryptase, anti-CD68, and anti–IL-6.

Results

There was no statistically significant difference in the mean number of mast cells and macrophages when comparing superficial and deep regions of the fibrous capsule of the cysts. Mean number of mast cells on the superficial region of the fibrous capsule was higher in cysts showing intense superficial inflammation and exocytosis. Macrophages were more commonly found in areas showing IL-6 expression, and IL-6 was less expressed in deep regions of the fibrous capsule in cysts showing greater gross volume.

Conclusions

The results reinforced the participation of mast cells and macrophages in the pathogenesis of periapical cysts and suggested that IL-6 is not the major bone resorption mediator in larger periapical cysts.     

Prevalence of oral anticoagulation in atrial fibrillation

OBJECTIVES:

Atrial fibrillation is the most common sustained arrhythmia and is associated with poor outcomes, including stroke. The ability of anticoagulation therapy to reduce the risk of stroke has been well established; however, the prevalence of anticoagulation therapy use in the Public Health System is unknown. The aim of this study is to evaluate both the prevalence of anticoagulation therapy among patients with atrial fibrillation and the indications for the treatment.

METHODS:

In this cross-sectional study, we included consecutive patients who had atrial fibrillation documented by an electrocardiogram performed between September 2011 and March 2012 at a university hospital of the Public Health System. The variables analyzed included the risk of a thromboembolic event and/or bleeding, the use of antiplatelet or anticoagulation therapy, the location where the electrocardiogram report was initially reviewed and the specialty of the physician who initially reviewed it.

RESULTS:

We included 162 patients (mean age 68.9 years, 56% men). Hypertension (90.1%), heart failure (53.4%) and stroke (38.9%) were the most prevalent diseases found. Only 50.6% of the patients knew that they had atrial fibrillation. Regarding the use of therapy, only 37.6% of patients classified as high risk according to the CHADS2 scores and 35.5% according to the CHA2DS2VASc used oral anticoagulation. A presumptive diagnosis of heart failure and the fact that the electrocardiogram was evaluated by a cardiologist were the only independent predictors of the use of anticoagulants.

CONCLUSIONS:

Our study found a low prevalence of oral anticoagulation therapy among patients with atrial fibrillation and an indication for stroke prophylaxis for the use of this therapy, including among those with high CHADS2 and CHA2DS2VASc scores.