‘Aberrant localisation of Annexin A1 is associated with metastatic outcome in thin melanomas’

International audienc

Dietary Supplementation with a Low Dose of Polyphenol-Rich Grape Pomace Extract Prevents Dextran Sulfate Sodium-Induced Colitis in Rats

Dietary Supplementation with a Low Dose of Polyphenol-Rich Grape Pomace Extract Prevents Dextran Sulfate Sodium-Induced Colitis in Rat

Lemon Verbena Infusion Consumption Attenuates Oxidative Stress in Dextran Sulfate Sodium-Induced Colitis in the Rat

International audienceBackground Inflammatory bowel diseases (IBD) consist of an uncontrolled intestinal inflammation leading to mucosal disruption. This inflammation is accompanied by an excessive production of reactive oxygen species (ROS). Polyphenols are micronutrients with antioxidative and anti-inflammatory properties, and may play an interesting role in the prevention of intestinal inflammation. Lemon verbena (Aloysia triphylla) infusion is a popular herbal infusion rich in polyphenols (flavones and verbascoside).Aims This study evaluated the preventive effects of lemon verbena infusion consumption against mild-to-moderate dextran sulfate sodium (DSS)-induced colitis in rats.Methods Wistar rats drank water or lemon verbena infusion for 14 days. On day 15, half of the rats received DSS (4%) in their drink for 7 days. At the end of the experimental period, the colon was taken for histopathological examination and determination of myeloperoxidase (MPO) activity, antioxidant enzyme activities (superoxide dismutase [SOD], glutathione peroxidase [GPx], glutathione reductase [GR], catalase [CAT]), glutathione and lipid peroxidation. Lymphocyte populations were determined in blood, mesenteric nodes and Peyer's patches.Results Rats ingested daily 5.6 mu mol of polyphenols. DSS reduced food intake and induced colitis, as reflected by histological lesions and increased MPO activity. Although these alterations were not significantly counteracted by lemon verbena consumption, the herbal infusion increased colonic SOD activity and decreased lipid peroxidation (malondialdehyde). Other oxidative stress markers (GPx, GR, CAT, glutathione) were not significantly modified.Conclusion Our study shows that the preventive consumption of lemon verbena infusion offered some antioxidative protection during experimental colitis by stimulating SOD activity and decreasing lipid peroxidation

Etude des effets preventifs d'extraits de marc de raisin sur l'inflammation colique induite par le sulfate de dextran sodique (DSS) chez le rat Preventive effect of grape pomace extracts on Dextran sodium sulfate (DSS)-induced colitis in rats

présentation orale : Boussena A .De nombreuses études ont souligné l'effet protecteur des polyphénols vis-à-vis de diverses pathologies chroniques. Cette étude vise à évaluer et comparer les effets d'une supplémentation nutritionnelle en extraits de marc de raisin (EMR), riches en polyphénols, dans la prévention d'une inflammation colique chimio-induite chez le rat. Les EMRs sont issus de deux cépages (Pinot ou Alicante) et de deux procédés d'extraction (classique : C ou breveté : B). Pour cela, des rats Wistar (n=40) ont été nourris ad libitum durant 21 jours avec un régime semi-synthétique supplémenté ou non avec un EMR (Pinot-C, Alicante-C, Alicante-B). L'inflammation colique a été induite par administration de DSS à 4% dans l'eau de boisson pendant les 7 derniers jours. L'analyse histologique, la détermination de l'activité de la myéloperoxydase (MPO) et de la superoxyde dismutase (SOD) ont été réalisées au niveau colique. Différentes cytokines ont été dosées au niveau du côlon. L'expression des gènes de la NO-synthase inductible (iNOS) et de la cyclooxygénase-2 (COX-2) a été déterminée par qRT-PCR. Le DSS induit une inflammation colique caractérisée par une chute du gain pondéral et des lésions histologiques. Les EMRs (Alicante) permettent de maintenir le gain de poids et de limiter les atteintes histologiques. Les EMRs Alicante-B et Pinot-C diminuent l'activité de la MPO induite par le DSS et l'EMR Alicante-B augmente l'activité de la SOD au niveau colique. Tous les EMRs limitent l'augmentation des taux coliques de cytokines pro-inflammatoires induite par le DSS. Les EMRs diminuent l'expression des gènes COX-2 (Alicante-B) et iNOS (Alicante-C et Alicante-B). Ainsi, ces résultats montrent que la consommation à titre préventif d'EMRs pourrait limiter le développement de l'inflammation colique. Ces travaux sont réalisés dans le cadre d'une convention CIFRE avec le groupe 3inature (Saint-Bonnet-de-Rochefort)

Impact of basal diet on dextran sodium sulphate (DSS)-induced colitis in rats

International audienceDextran sodium sulphate (DSS)-induced colitis is a widely used model for inflammatory bowel disease. However, various factors including nutrition may affect the development of this colitis. This study aimed to compare and characterize the impact of purified and non-purified basal diets on the development of DSS-induced colitis in the rat. Wistar rats were fed a non-purified or a semi-synthetic purified diet for 21 days. Colitis was then induced in half of the rats by administration of DSS in drinking water (4 % w/v) during the last 7 days of experimentation. At the end of the experimental period, colon sections were taken for histopathological examination, determination of various markers of inflammation (myeloperoxidase: MPO, cytokines) and oxidative stress (superoxide dismutase: SOD, catalase: CAT, glutathione peroxidase: GPx and glutathione reductase: GRed activities), and evaluation of the expression of various genes implicated in this disorder. DSS ingestion induced a more marked colitis in animals receiving the purified diet, as reflected by higher histological score and increased MPO activity. A significant decrease in SOD and CAT activities was also observed in rats fed the purified diet. Also, in these animals, administration of DSS induced a significant increase in interleukin (IL)-1α, IL-1β and IL-6. In addition, various genes implicated in inflammation were over-expressed after ingestion of DSS by rats fed the purified diet. These results show that a purified diet promotes the onset of a more severe induced colitis than a non-purified one, highlighting the influence of basal diet in colitis development

Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity

International audienceNon-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using 1H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor

Specificities of Hepatocellular Carcinoma Developed on Non Alcoholic Fatty Liver Disease in Absence of Cirrhosis Revealed by Tissue 1H-NMR Spectroscopy

SESSION 6 - CANCER-RELATED MALNUTRITION, METABOLISM, DYSIMMUNITYBackground and aims:Epidemiologic studies suggest that NAFLD increases the risk of Hepato-Cellular Carcinoma (HCC),even in non-cirrhotic NAFLD. This underlying disease is reported in up to 40% HCC.To get insights into the biology of HCC in non-cirrhotic NAFLD and seek for putative cancer pathways, we performed metabolomics in HCC associated with cirrhosis and non-cirrhotic NAFLD.Methods:Metabolomics was performed using 1H-NMR Spectroscopy. The analysis included 28 pairs of HCC tissue and distant Non-Involved Tissue (NIT) collected from patients undergoing hepatectomy. HCC was associated with cirrhosis (n = 9), normal liver (n=6) or NAFLD (n = 13).Results:In HCC versus NIT, statistical analyses showed high level of lactate and phosphocholine and low level of glucose. Multivariate analysis of HCC groups showed increased level of β-hydroxybutyrate in HCC-Cirrhosis and increased level of glutamine in HCC-NAFLD. OPLS-DA models of HCC-cirrhosis vs NIT (either normal tissue or cirrhosis) and HCC-NAFLD vs NIT (either normal tissue or NAFLD) were constructed before comparing them in shared and unique structure (SUS) plots. From SUS-plots, HCC-Cirrhosis was characterized by high levels of β-hydroxybutyrate, tyrosine and phenylalanine, whereas HCC-NAFLD was characterized by high levels of glutamine/glutamate. Glutamine Synthetase (GS) immuno-staining was correlated with the NMR-spectroscopy glutamine quantification.Conclusion:This study provides evidence of metabolic specificities of HCC associated with non-cirrhotic NAFLD versus HCC associated with cirrhosis. These alterations could suggest activation of glutamine synthetase pathway in HCC-NAFLD and mitochondrial dysfunction in HCC-cirrhosis, that may be part of specific carcinogenic processe

Second-Line Treatment and Prognostic Factors in Neuroendocrine Carcinoma.

International audienceNeuroendocrine carcinomas (NEC) are aggressive malignant diseases. Etoposide-based rechallenge (EBR) and the prognostic role of Rb status in second-line chemotherapy (2L) have not been studied. The objectives of this study were to report the results of 2L including EBR as well as prognostic factors in a national retrospective multicenter study. NEC patients treated in 2L and further, with tissue samples available were included. Rb status and morphological classification were reviewed centrally. Among the 121 NEC patients (40% female, median age 61) included, there were 73 small cell NEC (60%), 34 large cell NEC (28%) and 14 NEC (not otherwise specified, 12%). Primary sites were lung (39%), gastro-enteropancreatic (36%), other (13%) and unknown (12%). Median Ki-67 index was 80%. Median progression-free survival (PFS) and overall survival (OS) under 2L were 2.1 and 6.2 months, respectively. No difference was observed between patients who received an "Adenocarcinoma-like" or a "Neuroendocrine-like" 2L or according to the Rb status. Thoracic primary was the only adverse prognostic factor for OS. EBR, administered to 31 patients, resulted in a 62% disease control rate with a median PFS and OS of 3.2 and 11.7 months respectively. In the 94 patients with a relapse-free interval ≥q 3 months after first-line platinum-etoposide, median OS was 12 months in patients who received EBR as compared to 5.9 months in patients who did not (p=0.043). EBR could be the best 2L option for patient with initial response to first line platinum-etoposide lasting at least 3 months. Rb status does not provide prognostic information in this setting

Annexin A1 in primary tumors promotes melanoma dissemination

International audienc