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A case of double bronchial typical carcinoid of the central type, with a nodal metastasis and paraneoplastic Cushing syndrome is reported. The case is remarkable because both the primary tumors and nodal metastasis were composed of a duoble cell population: one was arranged in nests, was argyrophilic, immunostained with PHE-5 monoclonal antibody, and contained neurosecretory granules; the other one was neither argyrophilic nor PHE-5-immunoreactive, but was strongly immunoreactive for S-100 protein, had a stellate morphology and was at the periphery of the nests of the other cells. The S-100 immunoreactive cells were regarded as a sort of « sustentacular » or « satellite » cells, which are themselves neoplastic. Bronchial carcinoids with S-100 positive cells, although strictly related with other bronchial carcinoids, may in fact represent a group of tumors with different histogenesis and/or differentiative pattern. More work should be done to elucidate whether there is any relevant clinical difference between bronchial carcinoids with or without S-100 reactive cells.

Anomalous microwave emission (AME) is detected in many astrophysical environments as a foreground feature typically peaking between 20–30 GHz and extending over a 10–60 GHz range. One of the leading candidates for the source of AME is small spinning dust grains. Such grains should be very small (approx. ≤1 nm diameter) in order for the rotational emission to fall within the observed frequency range. In addition, these nanosized grains should possess a significant dipole moment to account for the observed emissivities. These constraints have been shown to be compatible with spinning bare nanosilicate clusters, assuming that ∼1% of the total Si mass budget is held in these ultrasmall grains. Silicate dust can be hydroxylated by processing in the interstellar medium and is generally known to provide seeds for molecular water ice nucleation in denser regions. Herein, we use quantum chemical calculations to investigate how the dipole moment of Mg-rich pyroxenic (MgSiO3) nanoclusters is affected by both accretion of molecular water and dissociative hydration. Our work thus provides an indication of how the formation of water ice mantles is likely to affect the capacity of nanosilicates to generate AME.

(2009). Ki67 cytoplasmic expression: Observations in normal tissue from heart atrial appendages of healthy rats. Cell Cycle: Vol. 8, No. 13, pp. 2125-2125.

The role of growth factors/receptors in the etiopathology and/or development of gastric cancer has recently come under scrutiny, since overexpression or amplification of the EGF system has been found in many intestinal type gastric cancers and related to a more aggressive behavior. Since these gastric carcinomas appear to develop from intestinal metaplasia, a study was planned to investigate whether overexpression of the EGF-receptor gene also occurred in intestinal metaplastic mucosa.Patients underwent upper GL endoscopy. Gastric biopsies for routine histology, Helicobacter pylori detection, quantification of intestinal metaplasia and EGF-R expression analysis were performed. A 30mer EGF-R specific oligonucleotide was end-labeled and used to probe a dot blot filter containing the RNA from the bioptic samples.Though all the gastric samples transcribed the EGF-R gene to a detectable level, overexpression of the EGF-R gene was found in the metaplastic mucosa in a minority of patients.These preliminary findings suggest that overexpression of the EGF-R gene is infrequent in the metaplastic gastric mucosa.

// Andrea Di Cristofori 1,2,* , Stefano Ferrero 3,4,* , Irene Bertolini 1,3 , Gabriella Gaudioso 1,3 , Maria Veronica Russo 1,3 , Valeria Berno 5 , Marco Vanini 6 , Marco Locatelli 2 , Mario Zavanone 1,2 , Paolo Rampini 2 , Thomas Vaccari 7 , Manuela Caroli 2 and Valentina Vaira 3,5 1 Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy 2 Division of Neurosurgery, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy 3 Division of Pathology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy 4 Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy 5 Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy 6 Surgical Pathology Unit, St. Anna Hospital, Como, Italy 7 IFOM - The FIRC Institute of Molecular Oncology, Milan, Italy * These authors have equally contributed to this work Correspondence to: Manuela Caroli, email: // Valentina Vaira, email: // Keywords : glioblastoma, vacuolar H+-ATPase, bafilomycin A1, cancer stem cells, organotypic tissue cultures Received : January 16, 2015 Accepted : May 02, 2015 Published : May 22, 2015 Abstract The vacuolar H + ATPase (V-ATPase) is a proton pump responsible for acidification of cellular microenvironments, an activity exploited by tumors to survive, proliferate and resist to therapy. Despite few observations, the role of V-ATPase in human tumorigenesis remains unclear. We investigated the expression of ATP6V0C, ATP6V0A2, encoding two subunits belonging to the V-ATPase V0 sector and ATP6V1C, ATP6V1G1, ATPT6V1G2, ATP6V1G3, which are part of the V1 sector, in series of adult gliomas and in cancer stem cell-enriched neurospheres isolated from glioblastoma (GBM) patients. ATP6V1G1 expression resulted significantly upregulated in tissues of patients with GBM and correlated with shorter patients’ overall survival independent of clinical variables. ATP6V1G1 knockdown in GBM neurospheres hampered sphere-forming ability, induced cell death, and decreased matrix invasion, a phenotype not observed in GBM monolayer cultures. Treating GBM organotypic cultures or neurospheres with the selective V-ATPase inhibitor bafilomycin A1 reproduced the effects of ATP6V1G1 siRNA and strongly suppressed expression of the stem cell markers Nestin, CD133 and transcription factors SALL2 and POU3F2 in neurospheres. These data point to ATP6V1G1 as a novel marker of poor prognosis in GBM patients and identify V-ATPase inhibition as an innovative therapeutic strategy for GBM.

Synovial sarcoma is a rare malignancy occurring mainly in the extremities. Only seven cases have been described arising in the esophagus. All of them presented as a polypoid mass involving the upper third of the esophagus. A case of infiltrating synovial esophageal sarcoma simulating achalasia in a 63-year-old woman is reported. According to the literature, the location and the clinical pattern of this tumor are exceptional. The clinical features, pathologic findings, differential diagnosis, and management of this condition are discussed.

We performed an immunohistochemical analysis to investigate the expression of p53 protein in a panel of 18 laryngeal squamous cell carcinomas, 15 primary tumours and three in relapse, previously analysed by us for the presence of p53 gene mutations. Dysplastic and/or normal surrounding mucosa was evaluated in 15 different tumours. The results of our study are the following: (1) expression of p53 protein was observed in one out of five tumours positive for p53 gene mutations (20%) and in 10 out of 13 (80%) negative cases; (2), p53 protein over-expression was frequently observed in normal and/or dysplastic mucosa surrounding either wild-type (7/11) or mutated p53 tumours (2/4); (3), p53 immunoreactive cells showed a pattern of distribution in normal and mildly/ moderately dysplastic mucosa (basal layers), different from that in severely dysplastic mucosa (whole thickness). These data further support the hypothesis that p53 protein over-expression may be a marker of the earliest phases of multistep tumorigenesis in laryngeal squamous cell carcinoma.

Background Coeliac disease is characterised by villous atrophy, which usually normalises after gluten withdrawal. Sometimes the revaluation of duodenal histology is required during follow-up, even if the methodology for comparing duodenal histology before and after introducing a gluten-free diet is not yet established. Our aim was to evaluate a novel criterion to compare duodenal histology in coeliac disease before and after gluten withdrawal. Methods Duodenal biopsies from coeliac patients were retrospectively reviewed to compare duodenal histology at diagnosis and after at least one year on a gluten-free diet. Two different methods were used: the first was represented by the classical Marsh-Oberhuber score, the second compared the areas covered by each Marsh-Oberhuber grade and expressed as percentages, the final grade being calculated from the analysis of ten power fields per duodenal biopsy. Results Sixty-nine patients (17 males 52 females, age at diagnosis 36 ± 15 years) who underwent duodenal biopsies, were considered. According to the classical Marsh-Oberhuber scale, 32 patients did not present atrophy during follow-up while 37 showed duodenal atrophy, among whom 26 improved the grade of severity and 11 retained the same one. Of these latter, according to the second method, eight patients were considered improved, two showed a worsened duodenal damage and only one remained unchanged; the evaluation changed in 91 % of cases. Conclusions The proposed semi-quantitative approach (i.e. the second method) for the evaluation of histology at follow-up provides additional information about the progression/regression of the mucosal damage. Electronic supplementary material The online version of this article (doi:10.1186/s12876-015-0361-8) contains supplementary material, which is available to authorized users.

In the coldest (10–20 K) regions of the interstellar medium, the icy surfaces of interstellar grains serve as solid-state supports for chemical reactions. Among their plausible roles, that of third body is advocated, in which the reaction energies of surface reactions dissipate throughout the grain, stabilizing the product. This energy dissipation process is poorly understood at the atomic scale, although it can have a high impact on astrochemistry. Here we study, by means of quantum mechanical simulations, the formation of NH3 via successive H-additions to atomic N on water ice surfaces, paying special attention to the third-body role. We first characterize the hydrogenation reactions and the possible competitive processes (i.e., H-abstractions), in which the H-additions are more favorable than the H-abstractions. Subsequently, we study the fate of the hydrogenation reaction energies by means of ab initio molecular dynamics simulations. Results show that around 58%–90% of the released energy is quickly absorbed by the ice surface, inducing a temporary increase of the ice temperature. Different energy dissipation mechanisms are distinguished. One mechanism, more general, is based on the coupling of the highly excited vibrational modes of the newly formed species and the libration modes of the icy water molecules. A second mechanism, exclusive during the NH3 formation, is based on the formation of a transient H3O+/NH2 − ion pair, which significantly accelerates the energy transfer to the surface. Finally, the astrophysical implications of our findings relative to the interstellar synthesis of NH3 and its chemical desorption into the gas are discussed.

BackgroundClear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approach for understanding genetic mechanisms of cancer and the most sensitive for identifying cancer-related genes.ResultsWe performed the first integrated analysis of DNA and RNA profiles of RCC samples using Affymetrix technology. Using 100K SNP mapping arrays, we assembled a genome-wide map of DNA copy number alterations and LOH areas. We thus confirmed the typical genetic signature of RCC but also identified other amplified regions (e.g. on chr. 4, 11, 12), deleted regions (chr. 1, 9, 22) and LOH areas (chr. 1, 2, 9, 13). Simultaneously, using HG-U133 Plus 2.0 arrays, we identified differentially expressed genes (DEGs) in tumor vs. normal samples. Combining genomic and transcriptomic data, we identified 71 DEGs in aberrant chromosomal regions and observed, in amplified regions, a predominance of up-regulated genes (27 of 37 DEGs) and a trend to clustering. Functional annotation of these genes revealed some already implicated in RCC pathology and other cancers, as well as others that may be novel tumor biomarkers.ConclusionBy combining genomic and transcriptomic profiles from a collection of RCC samples, we identified specific genomic regions with concordant alterations in DNA and RNA profiles and focused on regions with increased DNA copy number. Since the transcriptional modulation of up-regulated genes in amplified regions may be attributed to the genomic alterations characteristic of RCC, these genes may encode novel RCC biomarkers actively involved in tumor initiation and progression and useful in clinical applications.