Tyrosine Kinase Inhibitors in EGFR-Mutated Large-Cell Neuroendocrine Carcinoma of the Lung A Case Report

Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a high-grade carcinoma belonging to the neuroendocrine tumors of the lung and is different from typical lung large-cell carcinoma. It represents about 3% of all pulmonary malignancies and is characterized by neuroendocrine cytologic features. The treatment usually is platinum-based chemotherapy, however the outcome remains poor. Therefore new therapeutic options are needed. Tyrosine kinase inhibitors have demonstrated greater efficacy and better tolerability than standard chemotherapy in non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations. EGFR gene mutations were also rarely identified in LCNEC. We report a patient with lung LCNEC activating EGFR mutations who showed an impressive response to gefitinib

Targeting VEGF-VEGFR Pathway by Sunitinib in Peripheral Primitive Neuroectodermal Tumor, Paraganglioma and Epithelioid Hemangioendothelioma: Three Case Reports

Sunitinib malate (Sutent™; Pfizer Inc., New York, N.Y., USA) is a small molecule kinase inhibitor with activity against a number of tyrosine kinase receptors, including vascular endothelial growth factor receptors, stem-cell factor receptor, and platelet-derived growth factor receptors alpha and beta. Sunitinib, registered for the treatment of renal cell carcinoma and gastrointestinal stromal tumors, has recently been approved for the treatment of patients with advanced pancreatic neuroendocrine tumors. Peripheral primitive neuroectodermal tumor (pPNET), paraganglioma (PGL) and epithelioid hemangioendothelioma (EHE) are rare tumors in which there is an overexpression of pro-angiogenic factors and in which a high intratumoral microvessel density is a significant poor prognostic factor. On the basis of this preclinical rationale and the lack of effective treatments in pre-treated advanced stages of these rare diseases, we report our interesting experience of pPNET, PGL and EHE treatment with sunitinib

Minerals content and distribution in milk from red deer (Cervus elaphus), fallow deer (Dama dama) and roe deer (Capreolus capreolus)

The characterization of milk from red deer (Cervus elaphus, ReD), fallow deer (Dama dama, FaD) and roe deer (Capreolus capreolus, RoD) was carried out in this study, focusing on mineral contents and their dis- tribution between the soluble and colloidal phases of milk. Individual milk samples were collected from 23 ReD hinds, 31 FaD does, and 5 RoD does. The concentrations (mg/100 g) of minerals in milk were as follows(mean±SD):Ca,ReD=273±33,FaD=234±46,RoD=418±101;P,ReD=191±15,FaD=158±16, RoD=316±46; Mg, ReD=18±2, FaD=29±7, RoD=24±2; Na, ReD=41±7, FaD=41±8, RoD=45±3; K,ReD=126±6,FaD=120±17,RoD=140±16.The%ofmineralsinthesolublephaseofmilkwereasfol- lows (mean±SD): Ca, ReD=27±6, FaD=27±3, RoD=22±3; P, ReD=30±6, FaD=28±6, RoD=30±1; Mg,ReD=57±10,FaD=55±9,RoD=51±15.Atmicellarlevel,thecontentsofCa,PandMg(mmol/100g casein) resulted as follow: Ca, ReD = 0.79 ± 0.12, FaD = 0.68 ± 0.16, RoD = 0.96 ± 0.15; P, ReD = 0.65 ± 0.10, FaD=0.54±0.09, RoD=0.83±0.08; Mg, ReD=0.05±0.01, FaD=0.08±0.01, RoD=0.06±0.02

Analysis of a nanoparticle-enriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis

Down syndrome (DS) is caused by the presence of part or all of a third copy of chromosome 21. DS is associated with several phenotypes, including intellectual disability, congenital heart disease, childhood leukemia and immune defects. Specific microRNAs (miRNAs/miR) have been described to be associated with DS, although none of them so far have 2 been unequivocally linked to the pathology. The present study focuses to the best of our knowledge for the first time on the miRNAs contained in nanosized RNA carriers circulating in the blood. Fractions enriched in nanosized RNA-carriers were separated from the plasma of young participants with DS and their non-trisomic siblings and miRNAs were extracted. A microarray- based analysis on a small cohort of samples led to the identification of the three most abundant miRNAs, namely miR-16-5p, miR-99b-5p and miR-144-3p. These miRNAs were then profiled for 15 pairs of DS and non-trisomic sibling couples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results identified a clear differential expression trend of these miRNAs in DS with respect to their non-trisomic siblings and gene ontology analysis pointed to their potential role in a number of typical DS features, including “nervous system development”, “neuronal cell body” and certain forms of “leukemia”. Finally, these expression levels were associated with certain typical quantitative and qualitative clinical features of DS. These results contribute to the efforts in defining the DS-associated pathogenic mechanisms and emphasize the importance of properly stratifying the miRNA fluid vehicles in order to probe biomolecules that are otherwise hidden and/or not accessible to (standard) analysis

Pediatric Hidradenitis Suppurativa: A Cross-Sectional Study on Clinical Features and Treatment Approaches

Background Hidradenitis suppurativa is uncommon in patients of pediatric age, and differentiation with adult-onset disease is controversial. Treatment of pediatric hidradenitis suppurativa is scarcely standardized, and specific guidelines are lacking. Objective We report the clinical features, relevant risk-factors, comorbidity profile, and treatment patterns of a hospital-based cohort of pediatric hidradenitis suppurativa Methods In a cross-sectional study data on patients' demographics, disease-specific characteristics, early/pre-pubertal onset of disease, comorbidities, and treatment management were retrieved. Reference population data and clinical data from the national hidradenitis suppurativa disease registry were used for comparison. Results From a database of 870 patients with hidradenitis, 71 (15 males and 56 females) patients aged <18 years (mean age: 15.3 years; range 8-17 years), with mild (Hurley I, 45.1%) and moderate-severe disease (Hurley II-III, 54.9%), were retrieved. Smoking (23.9%) and overweight/obese frequencies (59.2%) were higher than reference population standards. Patient's older age at baseline (OR 1.43, 95% CI: 1.01 to 2.02) and higher BMI (OR 1.26, 95% CI: 1.07-1.48) were the only factors associated with moderate-severe disease. Family history and early/pre-pubertal onset of disease were not associated with severity or extent of disease. Sebaceous-follicular comorbid conditions were associated with cigarette smoking (P = .002). Among 81 treatment courses, clindamycin-based and zinc-sulphate-based combination regimens were most frequently used (59.3%). Female preponderance, family history of disease and extensive involvement were significantly different from the general hidradenitis suppurativa population. Conclusions Pediatric hidradenitis suppurativa presents a clinical spectrum comparable to adult-onset disease. Increased preventive measures should target obesity and smoking in this population