Long-term feeding trials examining the incorporation of conjugated linolenic acids (CLnA) into the diet of laying hens are lacking. In the present study, we compared two diets in sixty-six red Sex-Link hens (33 hens/treatment), fed for 26 weeks. The control diet was high in oleic acid, while the test diet was high in α-linolenic acid (ALA) and punicic acid (PunA). No significant differences were observed between treatments for hens’ performance, egg weight and yolk weight. In contrast, dietary ALA and PunA resulted in a significant increase in n-3 PUFA, rumenic acid (RmA) and PunA contents in egg yolk, as well as in the liver, heart, muscle and adipose tissue of the hens. Other conjugated dienes resulting from the metabolism of PunA or RmA also accumulated in the egg yolk and tissues. Unlike DHA, w[hich was exclusively distributed in phospholipids, ALA, RmA and PunA were preferably distributed in triglycerides.
Alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), rumenic acid (RmA), and punicic acid (PunA) are claimed to influence several physiological functions including insulin sensitivity, lipid metabolism and inflammatory processes. In this double-blind randomized controlled trial, we investigated the combined effect of ALA, DHA, RmA and PunA on subjects at risk of developing metabolic syndrome. Twenty-four women and men were randomly assigned to two groups. Each day, they consumed two eggs enriched with oleic acid (control group) or enriched with ALA, DHA, RmA, and PunA (test group) for 3 months. The waist circumference decreased significantly (-3.17 cm; p < 0.001) in the test group. There were no major changes in plasma insulin and blood glucose in the two groups. The dietary treatments had no significant effect on endothelial function as measured by peripheral arterial tonometry, although erythrocyte nitrosylated hemoglobin concentrations tended to decrease. The high consumption of eggs induced significant elevations in plasma low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (p < 0.001), which did not result in any change in the LDL/HDL ratio in both groups. These results indicate that consumption of eggs enriched with ALA, DHA, RmA and PunA resulted in favorable changes in abdominal obesity without affecting other factors of the metabolic syndrome.
3595 Background: Immune checkpoint inhibitors demonstrated poor efficacy in MSS mCRC. Cetuximab (anti-EGFR inhibitor) could initiate, independently from RAS mutation, an immunogenic tumor cell death and mediate antitumor immune response. In this trial, we aim to explore the clinical efficacy and safety of avelumab (anti-PDL1) combined with cetuximab and irinotecan for treatment refractory MSS mCRC and to understand its mechanisms of action through associated translational research. Methods: AVETUXIRI trial (NCT03608046) enrols MSS, chemorefractory (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) mCRC patients in 2 cohorts (A: RAS-wt, n = 10 – B: RAS-mut, n = 13). Primary endpoints are safety and tumor response rate ((i)RECIST1.1). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). According to a Simon 2-stage design, 23 patients have been included in the first stage of the trial. Multiplex immunofluorescence and RNA sequencing were realized on metastasis biopsies performed before, during and after the treatment. Densities of CD3+ (T cells) and CD8+ (cytotoxic) were quantified and analyzed with to generate an immunoscore (IS). RNA-seq data was used to perform differential expression analysis (DESeq2), gene set enrichment analysis (GSEA), deconvolution analysis (ConsensusTME) and gene ontology analysis (GO). Results:: No unexpected safety signals were observed. 3/10 tumor responses were observed in cohort A, 0/13 in cohort B. DCR was 60.0% and 61.5% in cohort A and B, respectively. 6-months PFS and 12-months OS rates were respectively 40.0% and 50.0% (cohort A) and 38.5% and 46.2% (cohort B). Independently of RAS mutation, patients with a high IS (metastasis biopsy, baseline) had significantly higher tumor shrinkage (OR = 18.67 p = 0.019), median PFS (6.9 vs 3.4 months; HR = 0.16, p = 0.002) and median OS (13.7 vs 7.9 months, HR = 0.26, p = 0.009). Similarly, tumor shrinkage and survival outcome (PFS > 6 months, OS > 12 months) were associated with upregulation of an adaptive immune response signature (including Th1, chemokine, adhesion molecules, immune checkpoints and T-cell activation genes, p. adj = 0.009) and the GSEA hallmark of epithelial to mesenchymal transition (p. adj = 0.045). Few modifications of IS and gene expression profiles were observed on the different metastasis biopsies performed overtime in the included patients. Conclusions: AVETUXIRI met its preliminary primary efficacy endpoint for RAS-wt mCRC pts, justifying its current continuation. Encouraging survival data observed in RAS-mut cohort allow the opening of a new cohort (PFS as primary endpoint). IS and adaptive immune response signature evaluated on metastases biopsies were associated with treatment efficacy and survival. Clinical trial information: NCT03608046.
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