Hyperprogressive disease in advanced cancer patients treated with nivolumab: a case series study.

The aim of this retrospective study was to detail the main clinicopathological characteristics of advanced cancer patients exhibiting hyperprogressive disease (HPD) during immune checkpoint inhibitor (ICI) nivolumab as second- or third-line treatment. A cohort of patients starting second or third-line nivolumab for advanced cancer from 2016 to 2018 was identified from our institution IRB approved and prospectively collected registry. HPD was defined as at least two-fold increase in the tumor growth rate (TGR) during immunotherapy compared to TGR during the preimmunotherapy period. Overall, 47 patients were eligible for this analysis. HPD was observed in three patients (6%) with metastatic lung adenocarcinoma, metastatic urothelial transitional carcinoma, and metastatic hepatocellular carcinoma, respectively. These three patients showed a rapid clinical deterioration and survived less than 3.5 months from immunotherapy onset. Their chief preimmunotherapy characteristics were: age < 75 years, ≥2 metastatic sites, programmed death-ligand 1 < 50%, neutrophil-to-lymphocyte ratio > 3, and elevated lactate dehydrogenase. The results of the current study seem to reinforce the hypothesis that in some cases immunotherapy promotes a dramatic increase of TGR and may suggest possible clinical predictors of HPD during nivolumab.

Fruit juice drinks prevent endogenous antioxidant response to high-fat meal ingestion.

High-fat meals (HFM) induce metabolic stress, leading to the activation of protective mechanisms, including inflammation and endogenous antioxidant defences. In the present study, we investigated the effects of antioxidant-rich fruit juice drinks on the endogenous antioxidant response induced by HFM. In a double-blind, cross-over design (10 d washout), fourteen overweight volunteers were randomly assigned to one of the following interventions: HFM+500 ml placebo beverage (HFM-PB, free from fruit); HFM+500 ml antioxidant beverage 1 (HFM-AB1; apple, grape, blueberry and pomegranate juices and grape skin, grape seed and green tea extracts); HFM+500 ml antioxidant beverage 2 (HFM-AB2; pineapple, black currant and plum juices). HFM-PB consumption increased the plasma levels of thiols (SH) (4 h, P< 0·001) and uric acid (UA) (2 h, P< 0·01) and total radical-trapping antioxidant parameter (TRAP) (4 h, P< 0·01). Following the consumption of drinks, UA production was significantly reduced with respect to placebo beverage consumption 8 h after HFM-AB2 consumption (P< 0·05). SH levels were reduced 0·5 (P< 0·05), 1 (P< 0·05) and 2 h (P< 0·01) after HFM-AB1 consumption and 2, 4 and 8 h (P< 0·05) after HFM-AB2 consumption. Plasma TRAP (2 h, P< 0·001) and urinary ferric reducing antioxidant power (0-8 h, P< 0·01) were increased by HFM-AB1 consumption, the drink with the highest in vitro antioxidant capacity, but not by HFM-AB2 consumption. In urine, UA levels were significantly increased from basal levels after the consumption of HFM-PB and HFM-AB2. However, neither of the beverages increased the urinary excretion of UA with respect to the placebo beverage. In conclusion, the increase in UA and SH levels induced by HFM as part of an endogenous antioxidant response to postprandial stress can be prevented by the concomitant ingestion of antioxidant-rich fruit juice drinks.

Antioxidant and inflammatory response following high-fat meal consumption in overweight subjects.

PURPOSE: Postprandial metabolic stress as a consequence of ingestion of high-energy meals is recognized as an important risk factor for cardiovascular disease. The objective of this study was to evaluate the inflammatory and antioxidant response of the body to the acute ingestion of a high-fat meal (HFM). METHODS: Fifteen healthy overweight subjects were recruited for the study. After HFM consumption, plasma glucose, insulin, uric acid (UA), triglycerides (TG), total cholesterol (TC), thiols (SH), inflammatory cytokines (IL-6 and TNF-α) and dietary antioxidants were measured at 0, 0, 5, 1, 2, 4, 6 and 8 h points from ingestion. RESULTS: The ingestion of HFM induced significant increases in both TG and TC, with peaks at 4 h (p < 0.001) and 8 h (p < 0.01), respectively. IL-6 and TNF-α significantly increased postprandially, reaching maximum concentrations 8 h after meal consumption (p < 0.001). Whereas plasma concentrations of vitamins and carotenoids were not changed by HFM, SH and UA increased, peaking 2-4 h postingestion (p < 0.001 and 0.01, respectively). Increments of SH and UA were positively correlated with AUC for TG (Pearson coefficient 0.888, p < 0.001 and 0.923, p < 0.001, respectively). CONCLUSIONS: Present results indicate that as a consequence of an excess of dietary fat, the body responds through an inflammatory reaction, which is accompanied by an increment of endogenous antioxidant defenses, mediated by UA and SH, but not by vitamins C and E and carotenoids. Although further studies are needed, results of the current investigation represent novel findings on endogenous strategies of redox defense from fat overloads.

Consumption of mixed fruit-juice drink and vitamin C reduces postprandial stress induced by a high fat meal in healthy overweight subjects.

Postprandial stress induced by acute consumption of meals with a high fat content results in an increase of markers of cardiometabolic risk. Repeated acute dietary stress may induce a persistent low-grade inflammation, playing a role in the pathogenesis of functional gut diseases. This may cause an impairment of the complex immune response of the gastrointestinal mucosa, which results in a breakdown of oral tolerance. We investigated the effect of ingestion of a fruit-juice drink (FJD) composed by multiple fruit juice and extracts, green tea extracts and vitamin C on postprandial stress induced by a High Fat Meal (HFM) in healthy overweight subjects. Following a double blind, placebo controlled, cross-over design, 15 healthy overweight subjects were randomized to a HFM providing 1334 Kcal (55% fat, 30% carbohydrates and 15% proteins) in combination with 500 mL of a placebo drink (HFM-P) or a fruit-juice drink (HFM-FJD). Ingestion of HFM-P led to an increase in circulating levels of cholesterol, triglycerides, glucose, insulin, TNF-α and IL-6. Ingestion of HFM-FJD significantly reduced plasma levels of cholesterol and triglycerides, decreasing inflammatory response mediated by TNF-α and IL-6. Ingestion of a fruit-juice drink reduce markers of postprandial stress induced by a HFM.

High fat meal increase of IL-17 is prevented by ingestion of fruit juice drink in healthy overweight subjects.

An emerging role of IL-17 in the inflammatory response associated with pathogenesis of neurodegeneration has been recently suggested. However, though diet represents a key factor in the modulation of inflammatory processes, evidence is not currently available on the nutritional regulation of IL-17 in humans. In a double blind, randomized, placebo controlled, crossover study, we investigated the effect of High Fat Meal (HFM) on IL-17 circulating levels in presence of a placebo (HFM-P) or with a Fruit Juice Drink (HFM-FJD) composed of pineapple, blackcurrant and plum in fourteen healthy overweight humans. Fasting in the morning subjects ingested a test meal providing 1344 Kcal. Ingestion of HFM-P induced an inflammatory response mediated by TNF-α (p < 0.001), IL-6 (p < 0.001) and IL-17 (p < 0.01). Plasma IL-17 concentration significantly increased at 1 h (+2.6 ± 1.1 pg/ml), remaining high at 4 h (+2.98 ± 1.2 pg/ml), 6 h (+2.38 ± 0.6 pg/ml) and 8 h (+2.8 ± 0.9 pg/ml) (ANOVA for time-course p=0.009). When the HFM was consumed in the presence of the FJD a marked inhibition of IL-17 response to the HFM was observed (ANOVA between treatment p=0.037). We provided, for the first time, evidence on the role of diet in modulating IL-17 production in healthy overweight subjects.