No cytotoxicity or genotoxicity of graphene and graphene oxide in murine lung epithelial FE1 cells in vitro

Graphene and graphene oxide receive much attention these years, because they add attractive properties to a wide range of applications and products. Several studies have shown toxicological effects of other carbon‐based nanomaterials such as carbon black nanoparticles and carbon nanotubes in vitro and in vivo. Here, we report in‐depth physicochemical characterization of three commercial graphene materials, one graphene oxide (GO) and two reduced graphene oxides (rGO) and assess cytotoxicity and genotoxicity in the murine lung epithelial cell line FE1. The studied GO and rGO mainly consisted of 2–3 graphene layers with lateral sizes of 1–2 µm. GO had almost equimolar content of C, O, and H while the two rGO materials had lower contents of oxygen with C/O and C/H ratios of 8 and 12.8, respectively. All materials had low levels of endotoxin and low levels of inorganic impurities, which were mainly sulphur, manganese, and silicon. GO generated more ROS than the two rGO materials, but none of the graphene materials influenced cytotoxicity in terms of cell viability and cell proliferation after 24 hr. Furthermore, no genotoxicity was observed using the alkaline comet assay following 3 or 24 hr of exposure. We demonstrate that chemically pure, few‐layered GO and rGO with comparable lateral size (> 1 µm) do not induce significant cytotoxicity or genotoxicity in FE1 cells at relatively high doses (5–200 µg/ml). Environ. Mol. Mutagen. 57:469–482, 2016. © 2016 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc.     

Monitoring and Follow-up of Chronic Heart Failure: a Literature Review of eHealth Applications and Systems

In developed countries heart failure is one of the most important causes of death, followed closely by strokes and other cerebrovascular diseases. It is one of the major healthcare issues in terms of increasing number of patients, rate of hospitalizations and costs. The main aim of this paper is to present telemedicine applications for monitoring and follow-up of heart failure and to show how these systems can help reduce costs of administering heart failure. The search for e-health applications and systems in the field of telemonitoring of heart failure was pursued in IEEE Xplore, Science Direct, PubMed and Scopus systems between 2005 and the present time. This search was conducted between May and June 2015, and the articles deemed to be of most interest about treatment, prevention, self-empowerment and stabilization of patients were selected. Over 100 articles about telemonitoring of heart failure have been found in the literature reviewed since 2005, although the most interesting ones have been selected from the scientific standpoint. Many of them show that telemonitoring of patients with a high risk of heart failure is a measure that might help to reduce the risk of suffering from the disease. Following the review conducted, in can be stated that via the research articles analysed that telemonitoring systems can help to reduce the costs of administering heart failure and result in less re-hospitalization of patients.     

Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine–Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HR_Q4vsQ1 = 0.95, 95% CI: 0.73–1.23; P_trend = .97; and HR_{per doubling of resistin concentration} = 1.00; 95% CI: 0.84–1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.     

Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer

BackgroundThe immunoglobulin G1 (IgG₁) monoclonal antibody (MoAb) Cetuximab is active in metastatic colorectal cancer (mCRC) as first or subsequent lines of therapy. Efficacy seems restricted to KRAS wild-type tumours. IgG₁ may also induce antibody dependent cell mediated citotoxicity (ADCC) by recruitment of immune effector cells. ADCC is influenced by Fc gamma receptor (FcγR) polymorphisms. We investigated the association of FcγR polymorphisms and disease control rate (DCR) in mCRC patients treated with chemotherapy plus Cetuximab.Patients and methodsTumour tissues from 106 patients were screened for KRAS codon 12 and 13 mutations using a sensitive multiplex assay (DxS, Manchester, United Kingdom). NRAS (codons: 12, 13 and 61), PI3K (exon 20) and BRAF (exon 15) were analysed by direct sequencing. Fcγ RIIa and Fcγ RIIIa polymorphisms were genotyped by TaqMan assays.ResultsDCR was significantly higher in KRAS wild-type tumours (61% versus 39%, p = 0.049). In epidermal growth factor receptor (EGFR) downstream-mutated mCRC patients, those harbouring an FcγRIIa H/H genotype had a higher DCR than alternative genotypes (67% versus 33%, p = 0.017). By multivariate analysis, FcγRIIa-131H/H remained significantly correlated with DCR (p = 0.008).ConclusionFcγR polymorphisms may play a role in the clinical efficacy of Cetuximab in EGFR downstream mutated mCRC patients. Further research into Cetuximab immune-based mechanisms in KRAS-mutated patients seems warranted.     

Epidemiology and prevalence of oropharyngeal candidiasis in Spanish patients with head and neck tumors undergoing radiotherapy treatment alone or in combination with chemotherapy

Objective

To describe the oropharyngeal candidiasis (OPC) prevalence in Spanish patients with head and neck cancer undergoing radiotherapy, alone or combined with chemotherapy. Secondary objectives were to determine the prevalence of Candida species colonization, and to explore whether different Candida species colonizing the oral cavity and the treatment were associated with a higher prevalence of OPC.

Methods

This is an observational, cross-sectional, multicentre study, conducted in Spanish radiation oncology units. Patients were diagnosed with head and neck cancer and started a radiotherapy treatment alone or combined with chemotherapy at the moment of their inclusion (N?=?92).

Results

The OPC prevalence was 26?%. The identification of colonizing pathogens was performed in 49 patients, and Candida albicans was the dominant yeast (69?%), while non-albicans Candida was only found in 15 patients (31?%). Patients with C. albicans colonization had a significant higher prevalence of OPC compared to patients colonized by non-albicans Candida (p?=?0.0273), but no difference was found regarding the OPC prevalence in patients receiving only radiotherapy compared to patients with both radiotherapy and chemotherapy treatments.

Conclusions

Our data represent a step further in the knowledge of Candida species present in Spanish patients with head and neck tumors under radiation therapy. This is an essential step to manage the prophylaxis and treatment of OPC, since it might lead to severe clinical complications causing treatment interruption and, thus, representing a reduction in anti-tumor efficacy.