Painful oral aphthous-like lesions in patient with kidney cancer after target therapy and bisphosphonate administration: a case report of adverse drug reaction.

Aim. Tyrosine kinase inhibitors (TKIs) targeting tu- mor angiogenesis and mammalian target of rapamycin inhibitors (mTOR) are indicated for the management of several cancer types, as for renal cell carcinoma (RCC). Oral ulcerations are reported as common adverse drug reactions of mTOR inhibitors and are currently classified as mTOR inhibitor associated stomatitis (mIAS). Interestingly, these lesions appear as aphthous-like stoma- titis rather than the mucositis seen with chemotherapy agent. Case report. A 49 years old male patient underwent to the left radical nephrectomy in May 2014 for clear RCC. From July to October 2014 he was treated with Pazopanib, a tyrosine kinase inhibitor. In December 2014 the patient started the treatment with Zoledronic acid and Everolimus, an amino-bisphosphonates and an mTOR inhibitor, respectively. Everolimus administration was suspended on the 1st of January 2015 and resumed on the 4th of February. In February 2015, the patient referred to our department for acute pain of mouth floor and tongue; the onset of these symptoms was subse- quent to mTOR therapy. This pain compromised his oral functions (chewing, swallowing, phonetic) and quality of life. Intraoral examination showed aphthous-like lesions on both borders of the tongue and on the right side of the mouth floor. Local antiseptic (0.2% chlorhexidine rinse, twice daily for 1 week), 0.050 g clobetasol propionate cream (twice a day for 4 week, and one times a day for the following 4 weeks) and a wound-healing promoter (Mucosamin Spray®, twice a day for 2 weeks) were administered. Since the oncologist decided to not discontinue the target therapy, the patient continued local therapy until the end of the treatment with everolimus. After two weeks from the first visit, a complete healing of the oral mucosa was observed and the patient complained no pain. Conclusion. This case report confirms the recent view that target therapy with everolimus may induce the onset of aphthous-like stomatitis as adverse drug reaction. Therefore, diagnostic algorithms for stomatitis should include a careful drug history, emphasizing the focus also on oral adverse effects the new target cancer therapies

Real-time cell analysis by xCELLigence®: a new method for dynamic, quantitative measurement of adhesion and proliferation of cell lines

Objectives. In this study, we report the use of a real-time cell analysis (RTCA) test system, the xCELLigence® RTCA, as efficient tool for a fast growth kinetics analysis of cell lines. This new dynamic real-time monitoring and impedance-based assay allows for a combined measurement of cell adhesion, spreading and proliferation. Methods. We used four representative human OSCC derived cell lines, PE49, HSC2, HSC3 and PE15 cells. The measured impedance values could be correlated to characteristic cell culture behaviours. In parallel, were evaluated proliferation and cell viability of the cell lines by the 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Results. Through the analysis we were able to quantitatively characterize the growth kinetics of the cell lines. The results are in agreement with the analysis MTT and for us will be the basis for future studies with respect to these lines.Conclusions. The advantage of impedance-based measurements is mainly based on these continuous monitoring of cell responses for a broad range of different cells and with different parameters of culture. Therefore, the xCELLigence system can be used as a rapid monitoring tool for cellular viability and used for multiple applications, such as toxicity testing of xenobiotics, biocompatibility of dental materials, tests of invasion and migration using in vitro cell cultures

A SHELL MODEL TURBULENT DYNAMO

Turbulent dynamo phenomena, observed almost everywhere in astrophysical objects and also in the laboratory in the recent VKS2 experiment, are investigated using a shell model technique to describe magnetohydrodynamic turbulence. Detailed numerical simulations at very high Rossby numbers (α2 dynamo) show that as the magnetic Reynolds number increases, the dynamo action starts working and different regimes are observed. The model, which displays different large-scale coherent behaviors corresponding to different regimes, is able to reproduce the magnetic field reversals observed both in a geomagnetic dynamo and in the VKS2 experiment. While rough quantitative estimates of typical times associated with the reversal phenomenon are consistent with paleomagnetic data, the analysis of the transition from oscillating intermittent through reversal and finally to stationary behavior shows that the nature of the reversals we observe is typical of α2 dynamos and completely different from VKS2 reversals. Finally, the model shows that coherent behaviors can also be naturally generated inside the many-mode dynamical chaotic model, which reproduces the complexity of fluid turbulence, as described by the shell technique

Epirubicin. A new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature

BACKGROUND: Current knowledge indicate that epirubicin administration in late pregnancy is almost devoid of any fetal cardiotoxicity. We report a twin pregnancy complicated by breast cancer in which epirubicin administration was causatively linked to the death of one twin who was small for gestational age (SGA) and in a condition of oligohydramnios and determined the onset of a transient cardiotoxicity of the surviving fetus/newborn. CASE PRESENTATION: A 38-year-old caucasic woman with a dichorionic twin pregnancy was referred to our center at 20 and 1/7 weeks for a suspected breast cancer, later confirmed by the histopathology report. At 31 and 3/7 weeks, after the second chemotherapy cycle, ultrasound examination evidenced the demise of one twin while cardiac examination revealed a monophasic diastolic ventricular filling, i.e. a diastolic dysfunction of the surviving fetus who was delivered the following day due to the occurrence of grade II placental abruption. The role of epirubicin cardiotoxicity in the death of the first twin was supported by post-mortem cardiac and placental examination and by the absence of structural or genomic abnormalities that may indicate an alternative etiology of fetal demise. The occurrence of epirubicin cardiotoxicity in the surviving newborn was confirmed by the report of high levels of troponin and transient left ventricular septal hypokinesia. CONCLUSION: Based on our findings we suggest that epirubicin administration in pregnancy should be preceded by the screening of some fetal conditions like SGA and oligohydramnios that may increase its cardiotoxicity and that, during treatment, the diastolic function of the fetal right ventricle should be specifically monitored by a pediatric cardiologist; also, epirubicin and desamethasone for lung maturation should not be closely administered since placental effects of glucocorticoids may increase epirubicin toxicity

A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy

Abstract Background At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed. Methods Recurrent GBM patients have been treated with fotemustine 75-100 mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6 m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment. Results 163 recurrent GBM patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p = 0.0161) and in those who had undergone a second surgery (p = 0.0306). Conclusions FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.</p

ENDOCANNABINOIDS CB1 AND CB2: A POSSIBLE ROLE IN ORAL SQUAMOUS CELL CARCINOMA PATHOGENESIS

Aim. Cancer of the oral cavity is the eighth most common malignancy in the world. The disease is diagnosed after a considerable delay and predict the individual progression is difficult. The improvements of the therapy did not increased the rate of survival at 5 years, that is still about 50%. The identification of the possible markers that indicates the progression of the tumor is therefore necessary. Endocannabinoids may play an important role in the process of carcinogenesis in the oral mucosa. They are able to bind and activate specific membrane receptors coupled to G proteins, cannabinoid receptors CB1 and CB2. The purpose of this study is to evaluate the expression of CB1 and CB2 receptors in the development of oral cancer through the immunohistochemical study on samples of OSCC. Materials and methods. We selected 44 cases of patients with the primary tumor in the oral cavity. The stage of the tumor was classified according to the TNM system. The tumors grading was divided into I, II and III grade. The paraffin sections were analyzed by immunohistochemistry. The assessment of the immunoreactivity for CB1 and CB2 receptors was weak or strong. For quantitative analysis the expression of CB1 and CB2 receptors was evaluated in percentage with scale of values ??ranging from 0 to 100%. Results. The immunohistochemical examination of the samples analyzed showed the absence of expression of CB1 and CB2 receptors in normal mucosa, while peritumoral mucosa showed a weak expression in the vicinity of cancer and tumor mucosa showed an overexpression of receptors. Furthermore, the intensity of staining increased with the increase of the grading. It can be concluded that the strong immunoreactivity of CB1 and CB2 receptors is related to aggressive behavior of oral carcinoma. Conclusions. The analysis of endocannabinoids and their receptors on tissue biopsies taken from carcinoma of the oral cavity may therefore indicate future therapeutic targets and new prognostic biomarkers in these patients, especially in the early stages of the disease. The ultimate goal of this work is to indicate the possible role of CB1 and CB2 receptors such as tumor biomarker that may help in the early diagnosis of oral cancer and therefore contribute to reduce drastically the mortality of this disease

Metabolomics application for the design of an optimal diet

Precision nutrition is an emerging branch of nutrition science that aims to use modern omics technologies (genomics, proteomics, and metabolomics) to assess an individual’s response to specific foods or dietary patterns and thereby determine the most effective diet or lifestyle interventions to prevent or treat specific diseases. Metabolomics is vital to nearly every aspect of precision nutrition. It can be targeted or untargeted, and it has many applications. Indeed, it can be used to comprehensively characterize the thousands of chemicals in foods, identify food by-products in human biofluids or tissues, characterize nutrient deficiencies or excesses, monitor biochemical responses to dietary interventions, track long- or short-term dietary habits, and guide the development of nutritional therapies. Indeed, metabolomics can be coupled with genomics and proteomics to study and advance the field of precision nutrition. Integrating omics with epidemiological and clinical data will begin to define the beneficial effects of human food metabolites. In this review, we present the metabolome and its relationship to precision nutrition. Moreover, we describe the different techniques used in metabolomics and present how metabolomics has been applied to advance the field of precision nutrition by providing notable examples and cases

Whole-genome sequencing and SNV genotyping of 'Nebbiolo' (Vitis vinifera L.) clones

'Nebbiolo' (Vitis vinifera) is among the most ancient and prestigious wine grape varieties characterised by a wide genetic variability exhibited by a high number of clones (vegetatively propagated lines of selected mother plants). However, limited information is available for this cultivar at the molecular and genomic levels. The whole-genomes of three 'Nebbiolo' clones (CVT 71, CVT 185 and CVT 423) were re-sequenced and a de novo transcriptome assembly was produced. Important remarks about the genetic peculiarities of 'Nebbiolo' and its intra-varietal variability useful for clonal identification were reported. In particular, several varietal transcripts identified for the first time in 'Nebbiolo' were disease resistance genes and single-nucleotide variants (SNVs) identified in 'Nebbiolo', but not in other cultivars, were associated with genes involved in the stress response. Ten newly discovered SNVs were successfully employed to identify some periclinal chimeras and to classify 98 'Nebbiolo' clones in seven main genotypes, which resulted to be linked to the geographical origin of accessions. In addition, for the first time it was possible to discriminate some 'Nebbiolo' clones from the others

Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase