Clinical parameters to guide decision-making in elderly metastatic colorectal CANCER patients treated with intensive cytotoxic and anti-angiogenic therapy

Introduction: Bevacizumab addiction to triplet chemotherapy, according to FIr-B/ FOx schedule, as first-line treatment in young-elderly metastatic colorectal CANCER (MCRC) patients may be more effective. Tailored treatments show worse clinical outcome in unfit patients. Methods: Elderly patients were clinically evaluated according to age and comorbidity (Cumulative Illness Rating Scale) to select FIr-B/FOx regimen in fit or tailored treatments in unfit elderly. Limiting toxicity syndromes (LTS) were evaluated. Results: At 17 months follow-up, in 28 young-elderly patients treated with first line FIr-B/FOx: objective response rate (ORR) 79%, progression-free survival (PFS) 11 months, overall survival (OS) 21 months. Clinical outcome was not significantly different according to KRAS genotype. G3-4 toxicities were diarrhea 21%, mucositis 11%, neutropenia 11%. LTS were 46%, significantly more multiple than single site. At 8 months follow-up, in 37 unfit patients: ORR 37%, PFS 7 months, OS 13 months. PFS was significantly different in KRAS wild-type compared to mutant patients, while not OS. PFS and OS were significantly worse in KRAS c.35 G > A compared to wildtype and/or other mutant. Conclusions: Careful decision-making process including evaluation of patient's fitness, and individual safety should be included to select FIr-B/FOx intensive first line regimen in young-elderly MCRC patients. KRAS, and specifically c.35 G > A mutant genotype, may significantly affect clinical outcome in patients unfit for FIr-B/FOx

Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is associated with increased liver-related mortality. Disturbances in hepatic lipid homeostasis trigger oxidative stress and inflammation (ie, lipotoxicity), leading to the progression of NASH. This study aimed at identifying whether silibinin may influence the molecular events of lipotoxicity in a mouse model of NASH. Eight-week-old db/db mice were fed a methionine-choline deficient (MCD) diet for 4 weeks and treated daily with silibinin (20 mg/kg intraperitoneally) or vehicle. Liver expression and enzyme activity of stearoyl-CoA desaturase-1 and acyl-CoA oxidase, and expression of liver fatty acid-binding protein were assessed. Hepatic levels of reactive oxygen species, thiobarbituric acid-reactive substances (TBARS), 3-nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NFkB) activities were also determined. Silibinin administration decreased serum alanine aminotransferase and improved liver steatosis, hepatocyte ballooning, and lobular inflammation in db/db mice fed an MCD diet. Gene expression and activity of stearoyl-CoA desaturase-1 were reduced in db/db mice fed an MCD diet compared with lean controls and were increased by silibinin; moreover, silibinin treatment induced the expression and activity of acyl-CoA oxidase and the expression of liver fatty acid-binding protein. Vehicle-treated animals displayed increased hepatic levels of reactive oxygen species and TBARS, 3-NT staining, and iNOS expression; silibinin treatment markedly decreased reactive oxygen species and TBARS and restored 3-NT and iNOS to the levels of control mice. db/db mice fed an MCD diet consistently had increased NFkB p65 and p50 binding activity; silibinin administration significantly decreased the activity of both subunits. Silibinin treatment counteracts the progression of liver injury by modulating lipid homeostasis and suppressing oxidative stress-mediated lipotoxicity and NFkB activation in experimental NASH

Monoclonal antibodies for the treatment of non-haematological tumours: Update of an expanding scenario

Introduction: The identification of cell membrane-bound molecules with a relevant role in cancer cell survival prompted the development of moAbs to block the related pathways. In the last few years, the number of approved moAbs for cancer treatment has constantly increased. Many of these drugs significantly improved the survival outcomes in patients with solid tumours.Areas covered: In this review, all the FDA-approved moAbs in solid tumours have been described. This is an update of moAbs available for cancer treatment nowadays in comparison with the moAbs approved until few years ago. The moAbs under development are also discussed here.Expert opinion: The research on cancer antigens as therapeutic targets led to an expanding scenario of available treatment options in non-haematological malignancies. In a few years, the number of approved drugs has increased rapidly. Some of these agents are actually on label in combination with standard chemotherapy. Only some of them can be delivered as monotherapy. The research on these new drugs is addressing both the identification of further target molecules in key cancer-related pathways and the improvement of drug effectiveness by changing the affinity and the selectivity of a moAb relative to its target

Time-restricted feeding and metabolic outcomes in a cohort of Italian adults

Background: research exploring the effects of food timing and frequency on health and disease is currently ongoing. While there is an increasing body of scientific literature showing the potential health benefits of intermittent fasting (IF) in laboratory settings and in animals, studies regarding IF on humans are limited. Therefore, the objective of this research was to evaluate the relationship between the feeding/fasting time window and metabolic outcomes among adult individuals. Methods: dietary and demographic data of 1936 adult subjects living in the south of Italy were examined. Food frequency questionnaires (FFQ) were administered to determine the period of time between the first and the last meal of a typical day. Subjects were then divided into those with a time feeding window lasting more than 10 h, within 8 h (TRF-8) and within 10 h. Results: after adjustment for potential confounding factors related to eating habits (such as adherence to the Mediterranean diet, having breakfast/dinner), TRF-10 was inversely associated with being overweight/obese (OR = 0.05, 95% CI: 0.01, 0.07), hypertension (OR = 0.24, 95% CI: 0.13, 0.45), and dyslipidemias (OR = 0.26, 95% CI: 0.10, 0.63), while TRF-8 only with being overweight/obese (OR = 0.08, 95% CI: 0.04, 0.15) and hypertension (OR = 0.33, 95% CI: 0.17, 0.60). No associations were found with type-2 diabetes. Conclusions: individuals with a restricted feeding time window were less likely to be overweight, obese and hypertensive. Further studies are needed to clearly validate the results of the present study

Environmental Impact of Dietary Choices: Role of the Mediterranean and Other Dietary Patterns in an Italian Cohort

Background: Current scientific literature suggests healthy dietary patterns may have less environmental impact than current consumption patterns, but most of the studies rely on theoretical modeling. The aim of this study was to assess the impact on resources (land, water, and energy) use and greenhouse gas (GHG) emissions of healthy dietary patterns in a sample of Italian adults. Methods: Participants (n = 1806) were recruited through random sampling in the city of Catania, southern Italy. Dietary consumption was assessed through a validated food frequency questionnaire (FFQ); dietary patterns were calculated through dietary scores. The specific environmental footprints of food item production/processing were obtained from various available life-cycle assessments; a sustainability score was created based on the impact of the four environmental components calculated. Results: The contribution of major food groups to the environmental footprint showed that animal products (dairy, egg, meat, and fish) represented more than half of the impact on GHG emissions and energy requirements; meat products were the stronger contributors to GHG emissions and water use, while dairy products to energy use, and cereals to land use. All patterns investigated, with the exception of the Dietary Approach to Stop Hypertension (DASH), were linearly associated with the sustainability score. Among the components, higher adherence to the Mediterranean diet and Alternate Diet Quality Index (AHEI) was associated with lower GHG emissions, dietary quality index-international (DQI-I) with land use, while Nordic diet with land and water use. Conclusions: In conclusion, the adoption of healthy dietary patterns involves less use of natural resources and GHG emissions, representing eco-friendlier options in Italian adults

Potential therapeutic effects of natural heme oxygenase-1 inducers in cardiovascular diseases.

Significance: Many physiological effects of natural antioxidants, their extracts or their major active components, have been reported in recent decades. Most of these compounds are characterized by a phenolic structure, similar to that of α-tocopherol, and present antioxidant properties that have been demonstrated both in vitro and in vivo. Polyphenols may increase the capacity of endogenous antioxidant defenses and modulate the cellular redox state. Such effects may have wide-ranging consequences for cellular growth and differentiation. Critical Issues: The majority of in vitro and in vivo studies conducted so far have attributed the protective effect of bioactive polyphenols to their chemical reactivity toward free radicals and their capacity to prevent the oxidation of important intracellular components. One possible protective molecular mechanism of polyphenols is nuclear factor erythroid 2-related factor (Nrf2) activation, which in turn regulates a number of detoxification enzymes. Recent Advances: Among the latter, the heme oxygenase-1 (HO-1) pathway is likely to contribute to the established and powerful antioxidant/anti-inflammatory properties of polyphenols. In this context, it is interesting to note that induction of HO-1 expression by means of natural compounds contributes to prevention of cardiovascular diseases in various experimental models. Future Directions: The focus of this review is on the role of natural HO-1 inducers as a potential therapeutic strategy to protect the cardiovascular system against various stressors in several pathological conditions

Total nut, tree nut, and peanut consumption and metabolic status in southern Italian adults

Background: Nut consumption has been associated with cardio-metabolic health benefits. However, studies conducted in the Southern Italian population, where adherence to the Mediterranean diet has been reported being relatively high, are rather scarce. The aim of this study was to test the association between consumption of total and specific types of nuts and metabolic status among adults living in Sicily, Southern Italy. Methods: Demographic and dietary characteristics of 2044 adults living in Southern Italy were analyzed. Multivariate logistic regression analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between nut consumption and metabolic status adjusting for potential confounding factors. Results: The energy-adjusted model revealed that higher nut intake was inversely associated with occurrence of hypertension, type-2 diabetes, and dyslipidemia. However, the association did not remain significant for the latter after adjusting for the main background characteristics, while an inverse association was stably confirmed for hypertension (OR = 0.61, 95% CI: 0.46–0.80 and OR = 0.44, 95% CI: 0.26–0.74, respectively) even after adjusting for adherence to the Mediterranean diet. Among individual nut types, most of the associations were null except for higher almond intake, which was inversely associated with occurrence of hypertension (OR = 0.70, 95% CI: 0.49–0.99). Conclusions: Higher nut consumption is associated with overall better metabolic status in individuals living in the Mediterranean area

Monoclonal antibodies in gastrointestinal cancers

none11noIntroduction: Among gastrointestinal cancers, colorectal and gastric neoplasms are the most frequent. The development of new targeted drugs improved the efficacy of systemic therapy in advanced stages of those malignancies. Areas covered: This review highlights the main biological processes implicated in gastrointestinal cancer development and progression, such as angiogenesis and epidermal growth factor receptor (EGFR) signaling pathway. On these bases, anti-EGFR and anti-vascular endothelial growth factor (VEGF) monoclonal antibodies in colorectal and gastric cancer are discussed. Data about further monoclonal antibodies in development are also reported. Expert opinion: The use of monoclonal antibodies in colorectal and gastric cancers showed the best outcomes when combined with chemotherapy, even though single agent anti-EGFR antibodies seem active in particular setting of metastatic colorectal cancer (CRC) patients. It is not well defined whether the addition of anti-VEGF and anti-EGFR to chemotherapy could improve outcome in those patients susceptible to CRC-related metastases resection. Little and conflicting data are available about the role of these drugs in adjuvant setting. Tests are available to select patients with higher probability to get benefit from these treatments. Further biomarkers need to be evaluated to improve this selection and achieve "tailorization" of systemic therapy. © 2013 Informa UK, Ltd.openBronte G.; Cicero G.; Cusenza S.; Galvano A.; Musso E.; Rizzo S.; Sortino G.; Roselli M.; Bazan V.; Fiorentino E.; Russo A.Bronte, G.; Cicero, G.; Cusenza, S.; Galvano, A.; Musso, E.; Rizzo, S.; Sortino, G.; Roselli, M.; Bazan, V.; Fiorentino, E.; Russo, A

Impact of chronic diuretic treatment on glucose homeostasis

Background The use of diuretics for hypertension has been associated with unfavorable changes in cardiovascular risk factors, such as uric acid and glucose tolerance, though the findings in the literature are contradictory. Methods This study investigated whether diuretic use is associated with markers of metabolic and cardiovascular risk, such as insulin-resistance and uric acid, in a cohort of adults without known diabetes and/or atherosclerotic cardiovascular disease. Nine hundred sixty-nine randomly selected participants answered a questionnaire on clinical history and dietary habits. Laboratory blood measurements were obtained in 507 participants. Results Previously undiagnosed type 2 diabetes was recognized in 4.2% of participants who were on diuretics (n = 71), and in 2% of those who were not (n = 890; P = 0.53). Pre-diabetes was diagnosed in 38% of patients who were on diuretics, and in 17.4% (P < 0.001) of those who were not. Multivariate analysis showed that insulin-resistance (HOMA-IR) was associated with the use of diuretics (P = 0.002) independent of other well-known predisposing factors, such as diet, physical activity, body mass index, and waist circumference. The use of diuretics was also independently associated with fasting plasma glucose concentrations (P = 0.001) and uric acid concentrations (P = 0.01). Conclusions The use of diuretics is associated with insulin-resistance and serum uric acid levels and may contribute to abnormal glucose toleranc