Dysphagia-related mucositis in children undergoing chemotherapy: The COMEDY pattern

Objectives Children undergoing chemotherapy can experience dysphagia due to non-erosive reflux disease (NERD). Oral mucositis (OM) associated with NERD-dysphagia in children with cancer has recently been defined with the acronym COMEDY (Clenching, Oral Mucositis, closed Eyes, DYsphagia). This study aims to identify the prevalence of the COMEDY pattern among chemotherapy-induced OM. Subjects and methods Forty-two medical records of children undergoing chemotherapy for haemato-oncologic diseases and presenting OM were reviewed. The following data were collected: age, type of haemato-oncologic disease, presence of dysphagia, type of oral mucosal lesions (i.e. traditional oral mucositis or COMEDY pattern), site of oral lesions, ear-nose-throat (ENT) assessment for the indirect signs of NERD and paediatric neuro-psychiatric (PNP) assessment. Results Among 42 children with chemotherapy-related OM, 6 patients (14.2%) showed the COMEDY pattern. Besides the characteristic clinical aspect of the oral mucosa, initially classified as grade II OM, these children suffered from NERD-related dysphagia and PNP issues. Conclusion A COMEDY pattern can occur in a number of cases of chemotherapy-induced OM; recognizing this pattern may improve the effectiveness of treatment

Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma

Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity. However, their ability to target the CSC compartment in melanoma is not known. Here we show that phenformin, but not metformin, strongly reduces melanoma cell viability, growth and invasion in both 2D and 3D (spheroids) models. While phenformin decreases melanoma CSC markers expression and the levels of the pro-survival factor MITF, MITF overexpression fails to prevent phenformin effects. Phenformin significantly reduces cell viability in melanoma by targeting both CSC (ALDHhigh) and non-CSC cells and by significantly reducing the number of viable cells in ALDHhighand ALDHlowderived spheroids. Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels. Our results show that phenformin is able to affect both CSC and non-CSC melanoma cell viability and growth and suggests its potential use as anti-cancer therapy in melanoma

Updating our understanding of health-related quality of life issues in children with cancer: a systematic review of patient-reported outcome measures and qualitative studies

publishedVersionPaid open acces

Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target

© 2009 Albini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

factors underlying the development of chronic temporal lobe epilepsy in autoimmune encephalitis

Abstract Purpose Limbic encephalitis (LE) is an autoimmune condition characterized by amnestic syndrome, psychiatric features and seizures. Early diagnosis and prompt treatment are crucial to avoid long-term sequelae, including psycho-cognitive deficits and persisting seizures. The aim of our study was to analyze the characteristics of 33 LE patients in order to identify possible prognostic factors associated with the development of chronic epilepsy. Methods This is a retrospective cohort study including adult patients diagnosed with LE in the period 2010–2017 and followed up for ≥12 months. Demographics, seizure semiology, EEG pattern, MRI features, CSF/serum findings were reviewed. Results All 33 LE patients (19 M/14F, mean age 61.2 years) presented seizures. Thirty subjects had memory deficits; 22 presented behavioural/mood disorders. Serum and/or CSF auto-antibodies were detected in 12 patients. In 31 subjects brain MRI at onset showed typical alterations involving temporal lobes. All patients received immunotherapy. At follow-up, 13/33 had developed chronic epilepsy; predisposing factors included delay in diagnosis (p = .009), low seizure frequency at onset (p = .02), absence of amnestic syndrome (p = .02) and absence/rarity of inter-ictal epileptic discharges on EEG (p = .06). Conclusions LE with paucisymptomatic electro-clinical presentation seemed to be associated to chronic epilepsy more than LE presenting with definite and severe "limbic syndrome"

Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement

Aortic enlargement in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD study

Background: The prevalence of abdominal aortic aneurysm is high in chronic obstructive pulmonary disease (COPD) population. Emphysema involves proteolytic destruction of elastic fibers. Therefore, emphysema may also contribute to thoracic aorta dilatation. This study assessed aorta dilation in smokers stratified by presence of COPD, emphysema and airway thickening. Methods: Aorta diameters were measured on 3D magnetic resonance angiography in smokers recruited from the Multi-Ethnic Study of Atherosclerosis (MESA), the Emphysema and Cancer Action Project (EMCAP), and the local community. COPD was defined by standard spirometric criteria; emphysema was measured quantitatively on computed tomography and bronchitis was determined from medical history. Results: Participants (n = 315, age 58–79) included 150 with COPD and 165 without COPD, of whom 56% and 19%, respectively, had emphysema. Subjects in the most severe quartile of emphysematous change showed the largest diameter at all four aorta locations compared to those in the least severe quartiles (all p < 0.001). Comparing subjectswith andwithout COPD, aorta diameters were larger in participantswith severe COPD in ascending and arch (both p < 0.001), and abdominal aorta (p = 0.001). Chronic bronchitis and bronchial wall thickness did not correlate with aorta diameter. In subjects with emphysema, subjects with coexistence of COPD showed larger aorta than those without COPD in ascending (p=0.003), arch (p=0.002), and abdominal aorta (p=0.04). Conclusions: This study showed larger aorta diameter in subjects with COPD and severe emphysema

Genomics and proteomics approaches to the study of cancer-stroma interactions

<p>Abstract</p> <p>Background</p> <p>The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.</p> <p>Methods</p> <p>The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.</p> <p>Results</p> <p>We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (<it>ARID4A</it>, <it>CALR</it>, <it>GNB2L1</it>, <it>RNF10</it>, <it>SQSTM1</it>, <it>USP9X</it>) were validated by real time PCR.</p> <p>Conclusions</p> <p>A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.</p

Multilinguisme et variétés linguistiques en Europe à l’aune de l’intelligence artificielle Multilinguismo e variazioni linguistiche in Europa nell’era dell’intelligenza artificiale Multilingualism and Language Varieties in Europe in the Age of Artificial Intelligence

Il presente volume è il frutto di una riflessione interdisciplinare e multilingue maturata attorno a diversi eventi organizzati nell’ambito del panel concernente i diritti e le variazioni linguistiche in Europa nell’era dell’intelligenza artificiale all’interno del progetto Artificial Intelligence for European Integration, promosso dal Centro studi sull’Europa TO-EU dell’Università di Torino e cofinanziato dalla Commissione europea. L’interrogativo iniziale che abbiamo voluto sollevare è se l’IA potesse avere un impatto negativo sulle varietà linguistiche e sul multilinguismo, valore “aggiunto” dell’UE, o se potesse, e in che modo, divenire utile per la promozione di essi. Il volume, interamente inedito, può dirsi tra i primi ad affrontare, almeno in Europa, questo tipo di tematiche.This book is the outcome of an interdisciplinary multilingual reflection carried out on research into linguistic rights, multilingualism and language varieties in Europe in the age of artificial intelligence. It is part of the Artificial Intelligence for European Integration project, promoted by the Centre of European Studies To-EU of the University of Turin and co-financed by the European Commission. Our aim was to investigate more generally the negative and/or positive outcomes of AI on language varieties and multilingualism, the latter a key value for the EU. The result is a volume of original unpublished research being made generally available for the first time, at least in Europe.Ce livre a été élaboré à partir d’une réflexion interdisciplinaire et multilingue qui a été menée dans le cadre d’une recherche sur les droits, le multilinguisme et les variétés linguistiques en Europe à l’aune de l’intelligence artificielle à l’intérieur du projet Artificial Intelligence for European Integration promu par le Centre d’études européennes To-EU de l’Université de Turin et cofinancé par la Commission de l’Union européenne. Notre propos était de réfléchir plus généralement sur les conséquences négatives et/ou positives de l’IA sur les variétés linguistiques et le multilinguisme, ce dernier étant une valeur de l’UE. Ce que nous proposons par ce numéro est un livre inédit qui peut se vanter d’être parmi les premiers à s’occuper de ce type de thématique, du moins en Europe