Vincenzo Quagliariello

Diabetes and Body Mass Index Are Associated with Neuropathy and Prognosis in Colon Cancer Patients Treated with Capecitabine and Oxaliplatin Adjuvant Chemotherapy

Background: There are few background data on the impact of clinical factors on neurotoxicity and prognosis in patients treated with adjuvant capecitabine and oxaliplatin (CAPOX) chemotherapy. Methods: 102 stage II high-risk and stage III colorectal cancer patients were treated for 6 months with adjuvant CAPOX, then they were followed up. Associations between clinical variables, metabolic syndrome components, smoking and neurotoxicity were evaluated by the χ2 test. The Kaplan-Meier product limit method was applied to graph disease-free survival (DFS). Univariate analysis was done with the log-rank test. Coxs proportional hazards regression was used to analyze the effect of several risk factors on DFS. Results: Significant associations were found between diabetes (p < 0.001), BMI (p = 0.01) and the occurrence of chronic neurotoxicity. After a median follow-up of 46 months, 14 patients (13.7%) had suffered recurrence. An analysis of the prognostic factors for DFS showed that prognosis is unfavorable for patients with high lymph-nodal involvement (HR: 5.23, p = 0.0007), diabetes (HR: 4.86; p = 0.03) and a BMI ≥25 (HR: 3.69, p = 0.002). Discussion: Common mediators in diabetes and obesity could be involved in peripheral neuropathy and in stimulating micro-metastases. Further studies are necessary to explain this interesting connection between diabetes, obesity and colon cancer.

Submicron complex lipid carriers for curcumin delivery to intestinal epithelial cells: Effect of different emulsifiers on bioaccessibility and cell uptake

Submicrometric lipid-based carriers were developed to encapsulate curcumin and deliver it to intestinal epithelial cells. A lipid matrix comprising monoolein, sunflower oil and water at weight ratio 1:1:1 was selected, upon screening of different combinations of amphiphilic molecules, vegetable oils and water, because of its high encapsulations efficiency of curcumin, retained over time and relatively lower content of amphiphilic molecules. Upon dispersion in aqueous phase, the carriers were stabilized by: (a) whey protein isolates (WPI), alone and (b) in combination with modified starch (WPI-MS), or by (c) polysorbate 20 (T20). Whereas T20-stabilized systems exhibited extremely fine particles (120 nm), WPI and WPI-MS stabilized carriers were characterized by a significantly larger mean particle size (270 nm). The thicker macromolecular layer of WPI and WPI-MS enabled better (a) physical stability, (b) controlled shell degradation during simulated digestion, and (c) curcumin bioaccessibility targeted at the intestinal digestion phase than T20-systems. However, uptake studies in HT29 cell lines, simulating intestinal epithelial cells, showed that WPI and WPI-MS carriers exhibited after 24h a lower relative uptake than T20-stabilized systems (about 60% and 80%, respectively), as a consequence of smaller size and higher cell adherence of T20 carriers to the cell membrane.

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

Anticancer and anti-inflammatory properties of ganoderma lucidum extract effects on melanoma and triple-negative breast cancer treatment

Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

Effect of pulsed electric fields – assisted extraction on anti-inflammatory and cytotoxic activity of brown rice bioactive compounds

The bioactive compounds of brown rice exhibit many beneficial health effects, ranging from antioxidant to cytotoxic activities. Pulsed Electric Field (PEF) pretreatment can significantly enhance their extraction, through the induction of the electro-permeabilization of the cell membranes. This paper aims to demonstrate that PEF-assisted extraction of brown rice enables not only enhanced yields of antioxidant compounds, such as γ-oryzanol, polyphenols and phenolic acids, and of saturated and unsaturated fatty acids, but also increased cytotoxic effects on cancer cells. Initially, the PEF-assisted extraction conditions have been defined by the assessment of the cell permeabilization index via impedance measurements and the DPPH antioxidant activity. Subsequently, the biological effects of PEF have been evaluated on the cytotoxicity and anti-inflammatory properties against human colon cancer cell line HT29. The results show that PEF-assisted extraction, enhancing the yield of bioactive compounds, with respect to untreated extracts, significantly promotes their antioxidant activity, which is correlated with an increased HT29 cells cytotoxicity. In addition, PEF extracts of brown rice substantially inhibit also gene expression and interleukin production in colon cancer cells, suggesting their exploitation as natural anti-inflammatory agents. The integration of PEF pretreatment in the solvent extraction process of bioactives from brown rice appears, therefore, as a promising practice to significantly enhance their biological activity.

Use of Complementary and Alternative Medicine (CAM) in cancer patients: An Italian multicenter survey

Introduction Complementary and Alternative Medicine (CAM) include a wide range of products (herbs, vitamins, minerals, and probiotics) and medical practices, developed outside of the mainstream Western medicine. Patients with cancer are more likely to resort to CAM first or then in their disease history; the potential side effects as well as the costs of such practices are largely underestimated. Patients and method We conducted a descriptive survey in five Italian hospitals involving 468 patients with different malignancies. The survey consisted of a forty-two question questionnaire, patients were eligible if they were Italian-speaking and receiving an anticancer treatment at the time of the survey or had received an anticancer treatment no more than three years before participating in the survey. RESULTS Of our patients, 48.9% said they use or have recently used CAM. The univariate analysis showed that female gender, high education, receiving treatment in a highly specialized institute and receiving chemotherapy are associated with CAM use; at the multivariate analysis high education (Odds Ratio, (OR): 1.96 95% Confidence Interval, CI, 1.27-3.05) and receiving treatment in a specialized cancer center (OR: 2.75 95% CI, 1.53-4.94) were confirmed as risk factors for CAM use. Conclusion Roughly half of our patients receiving treatment for cancer use CAM. It is necessary that health professional explore the use of CAM with their cancer patients, educate them about potentially beneficial therapies in light of the limited available evidence of effectiveness, and work towards an integrated model of health-care provision.

Hyaluronic Acid Nanohydrogel Loaded With Quercetin Alone or in Combination to a Macrolide Derivative of Rapamycin RAD001 (Everolimus) as a New Treatment for Hormone-Responsive Human Breast Cancer

The aim of this study is based on the evaluation of anticancer, anti‐inflammatory activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin tested alone and in combination to a macrolide derivative of rapamycin RAD001 (everolimus) on hormone‐responsive breast cancer cell line MCF‐7. Biological investigations were focused on the receptor mediated cellular internalization of the nanohydrogel and its abilities to reduce secretion of several cytokines (IL‐8, IL‐6, IL‐19), VEGF, and metalloproteases (MMP‐2, MMP‐9) under pro‐inflammatory conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time dependent cytoplasmatic accumulation with abilities to reduce secretion of all cytokines of ∼60% compared to untreated cells. Combination of formulated quercetin and everolimus leads to a synergistic cytotoxic effects with a Combination Index of 0.38. These results highlights the importance of synergistic effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the regulation of human breast cancer cell proliferation and emphasize the antitumor and anti‐inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063–2074, 2017.

Ectopic expression of gastrokine 1 in gastric cancer cells up-regulates tight and adherens junction proteins network.

Gastrokine 1 (GKN1) is a stomach-specific protein important in the replenishment of the surface lumen epithelial cell layer and in maintaining mucosal integrity. A role in cell proliferation and differentiation has also been hypothesized. Despite these findings, the function(s) as well as the cellular localization of GKN1 in the cellular machinery are currently not clarified. The investigation of subcellular localization of GKN1 in gastric cancer cells can provide insights into its potential cellular roles. Subcellular fractions of gastric cancer cells (AGS) transfected with full-length GKN1 (flGKN1) or incubated with recombinant GKN1 (rGKN1) lacking the first 20 amino acids at N-terminal were analyzed by Western blot and confocal microscopy and compared with those from normal gastric tissue. Wild type GKN1 (wtGKN1) and flGKN1 were revealed in the cytoplasm and in the membrane fractions of gastric cells, whereas rGKN1 was revealed in the cytoplasmic fractions, but a high amount was detected in the membrane pellet of the AGS lysate. The cellular distribution of GKN1 was also confirmed by confocal microscopy. The purified protein was also used to highlight its possible association with actin through confocal microscopy, pelleting assay, and size-exclusion chromatography. GKN1 co-localizes with actin in normal gastric tissue, but no direct interaction was observed between the two proteins in vitro. Most likely, GKN1 indirectly participates in actin stabilization since its overexpression in gastric cancer cells strongly increases the expression of tight and adherens junction proteins.

Oil/water nano-emulsion loaded with cobalt ferrite oxide nanocubes for photo-acoustic and magnetic resonance dual imaging in cancer: in vitro and preclinical studies

Dual imaging dramatically improves detection and early diagnosis of cancer. In this work we present an oil in water (O/W) nano-emulsion stabilized with lecithin and loaded with cobalt ferrite oxide (Co0.5Fe2.5O4) nanocubes for photo-acoustic and magnetic resonance dual imaging. The nanocarrier is responsive in in vitro photo-acoustic and magnetic resonance imaging (MRI) tests. A clear and significant time-dependent accumulation in tumor tissue is shown in in vivo photo-acoustic studies on a murine melanoma xenograft model. The proposed O/W nano-emulsion exhibits also high values of r2/r1 (ranging from 45 to 85, depending on the magnetic field) suggesting a possible use as T2 weighted image contrast agents. In addition, viability and cellular uptake studies show no significant cytotoxicity on the fibroblast cell line. We also tested the O/W nano-emulsion loaded with curcumin against melanoma cancer cells demonstrating a significant cytotoxicity and thus showing possible therapeutic effects in addition to the in vivo imaging.

CGRP and Visceral Pain: The Role of Sex Hormones in In-Vitro Experiment.

A large number of studies have showed that women reported feeling pain more acutely than men. In support of this hypothesis, many research groups proved that in different animals model of pain the sex hormones regulate the somatic and visceral sensitivity to different noxious stimuli. Therefore, in this study, we went to evaluate if estrogen hormones by regulating the CGRP levels are implicated during the visceral pain transmission. Toward this aim, we have investigated the effect of 17β‐estradiol in regulating the synthesis and release of CGRP, as well as the expression levels of the opioid receptor of type K. In order to gain information about the potential effects of 17β‐estradiol on K‐opioid receptor expression and activity, we have cultured F11 cells. Our results revealed that, when F11 cells were short‐term exposed (30 min) to 17β‐estradiol, the expression of the opioid K receptor was not significantly modified. We carried out enzyme immunoassay analysis to evaluate the potential effects of short‐term exposure to 17‐estradiol (30 min) on the release of CGRP in F11 cells. The results obtained showed that 17β‐estradiol at the dose of 100 nM is able to induce the release of CGRP from F11 cells; whereas, a higher dose of 17β‐estradiol (200 nM) did not produce significant effects when compared to control. In conclusion, all these findings suggest that the 17β‐estradiol‐regulated release of CGRP could at least in part provide a rational explanation for the difference of gender in the visceral pain sensitivity. J. Cell. Biochem. 118: 510–517, 2017.