Tumor–associated antigens identified by mRNA expression profiling as tumor rejection epitopes

Thirteen H-2(b)-binding peptides derived from six potentially overexpressed proteins in p53(-/- )thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after immunization, but only two of these peptides (RAD(23–31 )and RAD(24–31)) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take, suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD(23–31 )and RAD(24–31 )peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides derived from potentially overexpressed tumor proteins, as identified by mRNA expression profiling of p53(-/- )thymoma cells, at best results in a weak tumor protection thus questioning this way of detection of new tumor rejection epitopes

Effects of probiotics (Vivomixx®) in obese pregnant women and their newborn:Study protocol for a randomized controlled trial

BACKGROUND: Maternal obesity is associated with increased risks of adverse pregnancy-related complications and outcomes for both mothers and infants. Overweight and obese women have an increased risk of pregnancy-induced hypertension, preeclampsia and gestational diabetes mellitus (GDM). Infant Body Mass index (BMI) and the risk of obesity in adulthood are related to maternal gestational weight gain (GWG). Preventive lifestyle and dietary interventions are time-consuming and do not always reduce GWG or the risk of maternal pregnancy complications. Recent research has indicated that the gut microbiota may play a significant role in the development of obesity. Some studies have indicated that the daily consumption of probiotics may reduce the risk of preeclampsia, maintain serum insulin levels and reduce the frequency of GDM in pregnant women. The aims of this study are to investigate whether daily probiotic supplements in obese women during pregnancy can limit gestational weight gain, improve glucose homeostasis and thereby improve maternal, fetal and infant health outcomes. METHODS: A pilot study including 50 obese pregnant nulliparous women with a prepregnancy BMI of between 30 and 35 kg/m(2) will be randomized to receive daily probiotics (four capsules of Vivomixx®; total of 450 billion CFU/day, including eight probiotic bacterial strains) or placebo from gestational age 14–20 weeks until delivery. The infants will be followed until 9 months of age. The women will be monitored by weight, blood, fecal, vaginal and urine samples, diet questionnaires and hospital record review. Primary outcomes are: maternal weight gain, glycated hemoglobin (HbA1c) level and changes in glucose concentration measured during an oral glucose tolerance test. Secondary outcomes are: microbiota and inflammatory markers in mother and child, pregnancy complications, pregnancy outcomes, physical activity and the body composition of the neonate. DISCUSSION: We expect to find alterations in the metabolic profiles, microbiota and possibly pregnancy outcomes. From a clinical point of view the effects of Vivomixx® could control weight gain and reduce complications during pregnancy by inducing changes in the gut microbiota. Furthermore, this intervention during pregnancy could influence the infant’s microbiota, which could have important implications for infant development and health. TRIAL REGISTRATION: ClincalTrials.gov Identifier: NCT02508844, registered on 11 May 2015. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1617-5) contains supplementary material, which is available to authorized users

Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

Background : It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective : We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status. Methods : We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines. Inflammatory cytokines were investigated using a Th1/Th2 assay including 14 chemokines and cytokines; tissue concentrations were normalized according to tissue weight and total protein concentration. Individual cytokines and multivariate inflammatory profiles were compared between biopsy sites and between patients and controls. Results : We found significantly higher concentrations of Th2 cytokines in nasal polyps compared to inferior turbinate and bronchial biopsies. In addition, we showed that the inflammatory profile of nasal polyps and bronchial biopsies correlated significantly (p<0.01). From the Th2 cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma. Conclusion : Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally, this study indicates for the first time that nasal polyps potentially play an important role in the airway inflammation rather than being a secondary phenomenon