1,720,966 research outputs found
Combining Immune Checkpoint Inhibitors with Anti-Angiogenic Agents
No full textImmunotherapy has recently emerged as a novel strategy for treating different types of solid tumors, with promising results. However, still a large fraction of patients do not primarily respond to such approaches, and even responders sooner or later develop resistance. Moreover, immunotherapy is a promising strategy for certain malignancies but not for others, with this discrepancy having been attributed to a more immunogenic microenvironment of some tumors. As abnormal and augmented tumor vessels often occur in cancerogenesis, anti-angiogenic drugs have already demonstrated their effectiveness both in preclinical and in clinical settings. By targeting abnormal formation of tumor vessels, anti-angiogenetic agents potentially result in an enhanced infiltration of immune effector cells. Moreover, crosstalks downstream of the immune checkpoint axis and vascular endothelial growth factor receptor (VEGFR) signaling may result in synergistic effects of combined treatment in tumor cells. In this review, we will describe and discuss the biological rationale of a combined therapy, underlying the modification in tumor microenvironment as well as in tumor cells after exposure to checkpoint inhibitors and anti-angiogenic drugs. Moreover, we will highlight this strategy as a possible way for overcoming drug resistance. By first discussing potential prognostic and predictive factors for combined treatment, we will then turn to clinical settings, focusing on clinical trials where this strategy is currently being investigated
The Possible Role of Nutraceuticals in the Prevention of Cardiovascular Disease
Get PDFCardiovascular diseases (CVDs) are the main causes of mortality and disability worldwide. Although the initial therapeutic approach to improve the main cardiovascular (CV) risk factors is based on nonpharmacological measures, mainly lifestyle modifications, compliance to recommendations is often poor and inadequate. Therefore, in recent years the use of several nutraceuticals, i.e., nutrients and/or bioactive compounds of plant or microbial origin with potentially healthful effects, has become widespread. However, to date, the scientific data on the possible benefits of the use of nutraceuticals are still inconclusive, due to the absence of adequately controlled intervention studies at least for some of them. Against this background, the scientific evidence derived from controlled intervention studies in relation to the effects of some nutraceuticals (i.e. fiber, phytosterols, soy products, red yeast rice, polyphenols and berberine) on the main CV risk factors (body weight, blood pressure, blood glucose levels and plasma lipids) in humans will be reviewed
RET rearrangements in non-small cell lung cancer: Evolving treatment landscape and future challenges
No full textThe Rearranged during Transfection (RET) oncogene has been extensively investigated in solid malignancies, particularly thyroid cancer and non-small cell lung cancer (NSCLC), and represents an attractive therapeutic target. RET rearrangements occur in 1-2% of lung adenocarcinomas, where they function as potent oncogenic drivers. Importantly, tumors harboring RET fusions are particularly sensitive to RET tyrosine kinase inhibitors. Results of the LIBRETTO-001 and ARROW clinical trials led to the approval of novel potent and selective RET inhibitors, selpercatinib and pralsetinib, able to overcome the limits of previously used multikinase inhibitors. Herein, we review the most relevant evidences about the role of RET signaling in NSCLC. In addition, we interrogated the Project GENIE database to investigate common clinical and molecular features of RET-fusion positive NSCLC. This analysis revealed that RET rearrangements occurred more frequently in younger and light smoker patients and were associated with a lower tumor mutational burden, compared to RET-fusion negative tumors. Moreover, we assessed and described the differences between RET genomic alterations in NSCLC and thyroid cancers. Finally, we summarized how the treatment landscape of RET-rearranged NSCLC has changed in the last few years, which are the available data about the recognized mechanisms of resistance to RET inhibitors and the challenges for future development of novel therapeutic strategies, aiming to improve management of patients with RET-fusion positive NSCLC
Implementation of low glycemic index diet together with cornstarch in post-gastric bypass hypoglycemia: Two case reports
No full textPost-bariatric hypoglycemia (PBH) is an increasingly recognized long-term complication of bariatric surgery. The nutritional treatment of PBH includes a high-fiber diet and the restriction of soluble and high-glycemic index carbohydrates; however, these measures are not always enough to prevent hypoglycemia. We evaluated the efficacy of uncooked cornstarch, a low-glycemic index carbohydrate characterized by slow intestinal degradation and absorption, in addition to a high-fiber diet, for the treatment of PBH. We report the cases of two young women suffering from severe postprandial and fasting hypoglycemia following Roux-en-Y gastric bypass (RYGB). The patients underwent Continuous Glucose Monitoring (CGM) before and 12−16 weeks after the administration of uncooked cornstarch (respectively 1.25 g/kg b.w. and 1.8 g/kg b.w.) in addition to a high-fiber diet. In both patients, CGM showed more stable glucose levels throughout monitoring, a remarkable reduction of the time spent in hypoglycemia
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Effects of grape polyphenols on cardiometabolic risk factors
Get PDFPolyphenols are a heterogeneous group of compounds contained in plant foods. The main sources of polyphenols are whole grains, fruit, especially red fruits, soy, cocoa, tea, coffee and wine. The scientific interest for polyphenols is increasing thanks to epidemiological studies that suggest an association between the consumption of polyphenol-rich foods and prevention of some chronic-degenerative diseases, such as type 2 diabetes (DMT2), cardiovascular diseases (CVD) and several types of malignancies.
Polyphenols are reported to improve some biological functions, including endothelial function, platelet aggregation, lipid and glucose metabolism and to reduce oxidative stress. It is important to consider that the bioavailability of polyphenols, which is quite low (<10% of polyphenols or their metabolites are found in urine and plasma) influence their activities while their chemical structure influence their intestinal absorption. For these reasons, great attention is currently given to biovailability and structure of polyphenols.
Evidence on the beneficial effects of polyphenols mainly derive from in vitro and animal studies. These studies focused on the beneficial effects of the individual classes of polyphenols, in particular flavonoids. Moreover, these studies used pharmacological doses of these compounds that are difficult to obtain with the usual diet.
Red grape is a great source of polyphenols, especially anthocyanin and resveratrol. Acute studies demonstrated that grape polyphenols are able to reduce plasma glucose concentration in both animals and humans. Moreover, it has been observed an improvement in glucose metabolism after chronic consumption of grape polyphenols in subjects with the metabolic syndrome or type 2 diabetes. Grape supplementation seems to have also a favorable effect on others cardio-metabolic risk factors, such as plasma lipid levels, LDL oxidation and blood pressure.
In order to highlight the importance of grape polyphenols in the prevention of cardiovascular diseases, the present project was designed to assess: (1) the bioavailability of grape polyphenols and their plasma pharmacokinetic profile after assumption of phenolic-rich drink made from grape pomace; (2) the impact of grape polyphenols on some cardio-metabolic risk factors
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Impact of Grape Products on Lipid Profile: A Meta-Analysis of Randomized Controlled Studies
No full textBackground: Growing evidence shows that grape polyphenols can improve cardiovascular risk factors. Although there are clear data supporting a beneficial effect of grape supplementation on blood pressure and glucose metabolism, the effects of grape polyphenols on lipid metabolism are still controversial. Objective: We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of grape products on lipid profile. Design: A systematic search was performed in the PubMed, Web of Science, Scopus, and EMBASE databases without any language or publication year restriction. The reference lists of all retrieved articles were manually reviewed. RCTs evaluating the impact of grape products/juice/extracts on lipid profile were included. Difference in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), oxidized low-density lipoprotein cholesterol (oxLDL-C), apolipoprotein (apo) A, apo B before and after administration of grape products or placebo were expressed as mean differences (MD) with pertinent 95% confidence intervals (95% CI). The impact of clinical and demographic features on effect size was assessed by meta-regression. Results: The administration of grape products is associated with a significant improvement of lipid profile, as evidenced by changes in TC (MD: -7.6 mg/dL (-0.2 mmol/L); 95% CI: -10.8, -4.4; p < 0.001), HDL-C (MD: 1.4 mg/dL (0.04 mmol/L); 95% CI: 0.8, 1.9; p < 0.001, I2 = 74.7%, p < 0.001), LDL-C (-6.3 mg/dL (-0.16 mmol/L); 95% CI: -9.5, -3.0; p < 0.001), oxLDL-C (MD: -4.5 U/L; 95% CI: -7.5, -1.5; p = 0.003, I2 = 90.6%, p < 0.001), apo B (MD: -2.4 mg/dL (-0.05 μmol/L); 95% CI: -4.5, -0.3; p = 0.026), and TG (MD: -14.5 mg/dL (-0.16 mmol/L); 95% CI: -17.7, -11.2; p < 0.001) levels in subjects receiving grape products compared to placebo. With regard to the extent of the lipid-lowering effect, compared to baseline values, the highest reduction was reported for LDL-C (MD: -5.6 mg/dL (-0.14 mmol/L); 95% CI: -9.5, -1.7; p = 0.005) and for oxLDL-C (MD: -5.0 U/L; 95% CI: -8.8, -1.2; p = 0.010, I2 = 0%, p = 0.470). Conclusions: Grape polyphenols exert a favorable effect on lipid profile in humans by significantly reducing plasma levels of LDL-C and oxLDL-C
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