These findings suggested that KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab. In line with this, patients carrying KRAS mutations or with activated PI3K profiles can benefit from targeted treatments only by switching off molecules belonging to the downstream signalling of activated EGFR, such as mammalian target of rapamycin.

SummaryDietary polyphenols constitute a large family of bioactive substances potential beneficial effect on metabolic syndrome (MetS). This review summarizes the results of clinical studies on patients with MetS involving the chronic supplementation of a polyphenol-rich diet, foods, extracts or with single phenolics on the features of MetS (obesity, dyslipidemia, blood pressure and glycaemia) and associated complications (oxidative stress and inflammation). Polyphenols were shown to be efficient, especially at higher doses, and there were no specific foods or extracts able to alleviate all the features of MetS. Green tea, however, significantly reduced body mass index and waist circumference and improved lipid metabolism. Cocoa supplementation reduced blood pressure and blood glucose. Soy isoflavones, citrus products, hesperidin and quercetin improved lipid metabolism, whereas cinnamon reduced blood glucose. In numerous clinical studies, antioxidative and anti-inflammatory effects were not significant after polyphenol supplementation in patients with MetS. However, some trials pointed towards an improvement of endothelial function in patients supplemented with cocoa, anthocyanin-rich berries, hesperidin or resveratrol. Therefore, diets rich in polyphenols, such as the Mediterranean diet, which promote the consumption of diverse polyphenol-rich products could be an effective nutritional strategy to improve the health of patients with MetS.

Virgin olive oil (VOO) constitutes the main source of fat in the Mediterranean diet. VOO is rich in oleic acid, displaying health-promoting properties, but also contains minor bioactive components, especially phenolic compounds. Hydroxytyrosol (HT), the main polyphenol of olive oil, has been reported to be the most bioactive component. This review aims to compile the results of clinical, animal and cell culture studies evaluating the effects of HT on the features of Metabolic Syndrome (MetS) (body weight/adiposity, dyslipidemia, hypertension, and hyperglycemia/insulin resistance) and associated complications (oxidative stress and inflammation). HT was able to improve the lipid profile, glycaemia, and insulin sensitivity, and counteract oxidative and inflammatory processes. Experimental studies identified multiple molecular targets for HT conferring its beneficial effect on health in spite of its low bioavailability. However, rodent experiments and clinical trials with pure HT at biologically relevant concentrations are still lacking. Moreover, the roles of intestine and its gut microbiota have not been elucidated.

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Oxidative stress could trigger lipid accumulation in liver and thus hepatic steatosis. Tea is able to prevent liver disorders, but a direct link between antioxidant capacities and prevention of steatosis has not been reported yet. We aimed to investigate such relationship in a rat model of high fat-high sucrose diet (HFS)-induced obesity and to explore more deeply the mechanisms in isolated hepatocytes. Wistar rats were divided into a control group (standard diet), an HFS group (high fat-sucrose diet) and an HFS+tea group (HFS diet with ad-libitum access to tea drink). Body weight, fat mass, glycemic parameters in blood, lipid and oxidative stress parameters in blood and liver were measured in each group after 14 weeks. Isolated hepatocytes were treated with the reactive oxygen species (ROS) inducer t-BHP in the presence or not of antioxidants (tempol or tea), and superoxide anion production and lipid accumulation were measured using specific fluorescent probes. We reported that the HFS diet highly increased hepatic lipids content, while tea consumption attenuated steatosis and improved the oxidative status (decrease in hepatic oxidative stress, increase in plasma total antioxidant capacity). The role of antioxidant properties of tea in such phenomenon was confirmed in primary cultured rat hepatocytes. Indeed, the increase of mitochondrial ROS production with t-BHP resulted in lipid accumulation in hepatocytes (positive linear regression), and antioxidants (tempol or tea) normalized both. We reported that the antioxidant properties of tea protect rats from an obesogenic HFS diet-induced hepatic steatosis by counteracting the ROS-dependent lipogenesis.