Carcinoma de próstata com diferenciação neuroendócrina: relato de caso

Neuroendocrine differentiation in prostatic carcinomas generally confers a more aggressive clinical behavior and less favorable prognosis than usual prostatic carcinomas. In this manuscript, we report a case of a 58-year-old man with prostatic carcinoma who died 1 year after initial diagnosis. Autopsy showed a disseminated prostatic carcinoma with neuroendocrine differentiation. There were metastasis to the spleen, an organ infrequently involved by disseminated epithelial neoplasms. Neuroendocrine differentiation was demonstrated by immunohistochemical studies in the biopsy and autopsy material.Os carcinomas da próstata com diferenciação neuroendócrina apresentam comportamento mais agressivo e prognóstico menos favorável que as neoplasias prostáticas usuais. No presente relato de caso é reportada a rápida evolução para o óbito de um paciente de 58 anos portador de adenocarcinoma de próstata com diferenciação neuroendócrina. A autópsia mostrou neoplasia disseminada, acometendo inclusive o baço, sítio incomum de envolvimento metastático de neoplasias de origem epitelial. A diferenciação neuroendócrina foi demonstrada por estudo imunohistoquímico em material de biópsia e autópsia

Mutation profling of cancer drivers in Brazilian colorectal cancer

The molecular basis of colorectal cancer (CRC) can guide patient prognosis and therapy. In Brazil, knowledge on the CRC mutation landscape is limited. Here, we investigated the mutation profile of 150 cancer-related genes by next-generation sequencing and associated with microsatellite instability (MSI) and genetic ancestry in a series of 91 Brazilian CRC patients. Driver mutations were found in the APC (71.4%), TP53 (56.0%), KRAS (52.7%), PIK3CA (15.4%) and FBXW7 (10.9%) genes. Overall, genes in the MAPK/ERK, PIK3/AKT, NOTCH and receptor tyrosine kinase signaling pathways were mutated in 68.0%, 23.1%, 16.5%, and 15.3% of patients, respectively. MSI was found in 13.3% of tumors, most of which were proximal (52.4%, P< 0.001) and had a high mutation burden. European genetic ancestry was predominant (median of 83.1%), followed by Native American (4.1%), Asian (3.4%) and African (3.2%). NF1 and BRAF mutations were associated with African ancestry, while TP53 and PIK3CA mutations were inversely correlated with Native American ancestry. Our study suggests that Brazilian CRC patients exhibit a mutation profile similar to other populations and identify the most frequently mutated genes, which could be useful in future target therapies and molecular cancer screening strategies.We are thankful to Barretos Cancer Hospital. This work was supported by the Brazilian Federal Agency for the Support and Evaluation of Graduate Education (CAPES, Brazil), the National Council for Scientifc and Technological Development (CNPq, Brazil), and the Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer, Brazil)

Thermoelectric properties of lead chalcogenide core-shell nanostructures

We present the full thermoelectric characterization of nanostructured bulk PbTe and PbTe-PbSe samples fabricated from colloidal core-shell nanoparticles followed by spark plasma sintering. An unusually large thermopower is found in both materials, and the possibility of energy filtering as opposed to grain boundary scattering as an explanation is discussed. A decreased Debye temperature and an increased molar specific heat are in accordance with recent predictions for nanostructured materials. On the basis of these results we propose suitable core-shell material combinations for future thermoelectric materials of large electric conductivities in combination with an increased thermopower by energy filtering.Comment: 12 pages, 8 figure

Alternative lengthening of telomeres, ATRX loss and H3â K27M mutations in histologically defined pilocytic astrocytoma with anaplasia

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fiftyâ seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3â 75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomereâ specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3â K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRXâ (20/24, 83%) or ALTâ /ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3â K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PAâ A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3â K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/1/bpa12646_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/2/bpa12646.pd

Ram pressure stripping of disc galaxies orbiting in clusters. II. Galactic wakes

We present 3D hydrodynamical simulations of ram pressure stripping of a disc galaxy orbiting in a galaxy cluster. In this paper, we focus on the properties of the galaxies' tails of stripped gas. The galactic wakes show a flaring width, where the flaring angle depends on the gas disc's cross-section with respect to the galaxy's direction of motion. The velocity in the wakes shows a significant turbulent component of a few 100 km/s. The stripped gas is deposited in the cluster rather locally, i.e. within ~150 kpc from where it was stripped. We demonstrate that the most important quantity governing the tail density, length and gas mass distribution along the orbit is the galaxy's mass loss per orbital length. This in turn depends on the ram pressure as well as the galaxy's orbital velocity. For a sensitivity limit of ~10^19 cm^-2 in projected gas density, we find typical tail lengths of 40 kpc. Such long tails are seen even at large distances (0.5 to 1 Mpc) from the cluster centre. At this sensitivity limit, the tails show little flaring, but a width similar to the gas disc's size. Morphologically, we find good agreement with the HI tails observed in the Virgo cluster by Chung et al. (2007). However, the observed tails show a much smaller velocity width than predicted from the simulation. The few known X-ray and H$\alpha$ tails are generally much narrower and much straighter than the tails in our simulations. Thus, additional physics like a viscous ICM, the influence of cooling and tidal effects may be needed to explain the details of the observations. We discuss the hydrodynamical drag as a heat source for the ICM but conclude that it is not likely to play an important role, especially not in stopping cooling flows.Comment: 23 pages, 23 figures, accepted by MNRAS. Additions to method, result and discussion section, references added. Results and conclusions essentially unchanged. high resolution pdf available at http://www.faculty.iu-bremen.de/eroediger/PAPERS/eroediger_wakes.pd

Musculoskeletal Response to Whole-Body Vibration During Fracture Healing in Intact and Ovariectomized Rats

This study investigated the effect of vibration on bone healing and muscle in intact and ovariectomized rats. Thirty ovariectomized (at 3 months of age) and 30 intact 5-month old female Sprague-Dawley rats underwent bilateral metaphyseal osteotomy of tibia. Five days later, half of the ovariectomized and of the intact rats were exposed to whole-body vertical vibration (90 Hz, 0.5 mm, 4 × g acceleration) for 15 min twice a day during 30 days. The other animals did not undergo vibration. After decapitation of rats, one tibia was used for computed tomographic, biomechanical, and histological analyses; the other was used for gene expression analyses of alkaline phosphatase (Alp), osteocalcin (Oc), tartrate-resistant acid phosphatase 1, and insulinlike growth factor 1. Serum Alp and Oc were measured. Mitochondrial activity, fiber area and distribution, and capillary densities were analyzed in M. gastrocnemius and M. longissimus. We found that vibration had no effect on body weight and food intake, but it improved cortical and callus densities (97 vs. 99%, 72 vs. 81%), trabecular structure (9 vs. 14 trabecular nodes), blood supply (1.7 vs. 2.1 capillaries/fiber), and oxidative metabolism (17 vs. 23 pmol O2/s/mg) in ovariectomized rats. Vibration generally increased muscle fiber size. Tibia biomechanical properties were diminished after vibration. Oc gene expression was higher in vibrated rats. Serum Alp was increased in ovariectomized rats. In ovariectomized rats, vibration resulted in an earlier bridging; in intact rats, callus bridging occurred later after vibration. The chosen vibration regimen (90 Hz, 0.5 mm, 4 × g acceleration, 15 min twice a day) was effective in improving musculoskeletal tissues in ovariectomized rats but was not optimal for fracture healing

The bioenergetic role of dioxygen and the terminal oxidase(s) in cyanobacteria

AbstractOwing to the release of 13 largely or totally sequenced cyanobacterial genomes (see http://www.kazusa.or.jp/cyano and www.jgi.doe.gov/), it is now possible to critically assess and compare the most neglected aspect of cyanobacterial physiology, i.e., cyanobacterial respiration, also on the grounds of pure molecular biology (gene sequences). While there is little doubt that cyanobacteria (blue-green algae) do form the largest, most diversified and in both evolutionary and ecological respects most significant group of (micro)organisms on our earth, and that what renders our blue planet earth to what it is, viz. the O2-containing atmosphere, dates back to the oxygenic photosynthetic activity of primordial cyanobacteria about 3.2×109 years ago, there is still an amazing lack of knowledge on the second half of bioenergetic oxygen metabolism in cyanobacteria, on (aerobic) respiration. Thus, the purpose of this review is threefold: (1) to point out the unprecedented role of the cyanobacteria for maintaining the delicate steady state of our terrestrial biosphere and atmosphere through a major contribution to the poising of oxygenic photosynthesis against aerobic respiration (“the global biological oxygen cycle”); (2) to briefly highlight the membrane-bound electron-transport assemblies of respiration and photosynthesis in the unique two-membrane system of cyanobacteria (comprising cytoplasmic membrane and intracytoplasmic or thylakoid membranes, without obvious anastomoses between them); and (3) to critically compare the (deduced) amino acid sequences of the multitude of hypothetical terminal oxidases in the nine fully sequenced cyanobacterial species plus four additional species where at least the terminal oxidases were sequenced. These will then be compared with sequences of other proton-pumping haem–copper oxidases, with special emphasis on possible mechanisms of electron and proton transfer

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance