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https://www.readbyqxmd.com/read/28545085/splicing-factor-sf3b1k700e-mutant-dysregulates-erythroid-differentiation-via-aberrant-alternative-splicing-of-transcription-factor-tal1
#1
Shuiling Jin, Hairui Su, Ngoc-Tung Tran, Jing Song, Sydney S Lu, Ying Li, Suming Huang, Omar Abdel-Wahab, Yanyan Liu, Xinyang Zhao
More than 60% of myeloid dysplasia syndrome (MDS) contains mutations in genes encoding for splicing factors such as SF3B1, U2AF, SRSF2 and ZRSR2. Mutations in SF3B1 are associated with 80% cases of refractory anemia with ring sideroblast (RARS), a subtype of MDS. SF3B1K700E is the most frequently mutated site among mutations on SF3B1. Yet the molecular mechanisms on how mutations of splicing factors lead to defective erythropoiesis are not clear. SF3B1K700E mutant binds to an RNA binding protein, RBM15, stronger than the wild type SF3B1 protein in co-immunoprecipitation assays...
2017: PloS One
https://www.readbyqxmd.com/read/28544703/high-ubiquitin-specific-protease-44-expression-induces-dna-aneuploidy-and-provides-independent-prognostic-information-in-gastric-cancer
#2
Sho Nishimura, Eiji Oki, Koji Ando, Makoto Iimori, Yu Nakaji, Yuichiro Nakashima, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara
Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28544475/thiazole-based-sigma-1-receptor-ligands-diversity-by-late-stage-c-h-arylation-of-thiazoles-structure-affinity-and-selectivity-relationships-and-molecular-interactions
#3
Bernhard Wünsch, Artur Kokornaczyk, Dirk Schepmann, Junichiro Yamaguchi, Kenichiro Itami, Erik Laurini, Maurizio Fermeglia, Sabrina Pricl
Spirocyclic thiophene derivatives represent promising sigma-1 ligands with high sigma-1 affinity and selectivity over the sigma-2 subtype. In order to increase ligand efficiency, the thiophene ring was replaced bioisosterically by a thiazole ring and the pyran ring was opened. Late-stage diversification by regioselective C-H arylation of thiazoles 9a-c resulted in a set of 53 compounds with high diversity. This set of compounds was analyzed with respect to sigma-1 affinity, sigma-1/sigma-2 selectivity, lipophilicity (logD7...
May 24, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28544061/survival-difference-according-to-mutation-status-in-a-prospective-cohort-study-of-australian-patients-with-metastatic-non-small-cell-lung-carcinoma-nsclc
#4
Lavinia Tan, Marliese Alexander, Ann Officer, Michael MacManus, Linda Mileshkin, Ross Jennens, Dishan Herath, Richard de Boer, Stephen B Fox, David Ball, Benjamin Solomon
BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histologic subtypes but also different molecular subtypes. Our objective is to describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled onto a prospective Thoracic Malignancies Cohort (TMC) Study between July 2012 and August 2016 were selected...
May 24, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28542706/modulatory-features-of-the-novel-spider-toxin-%C3%AE-trtx-df1a-isolated-from-the-venom-of-the-spider-davus-fasciatus
#5
Fernanda C Cardoso, Zoltan Dekan, Jennifer J Smith, Jennifer R Deuis, Irina Vetter, Volker Herzig, Paul F Alewood, Glenn F King, Richard J Lewis
BACKGROUND AND PURPOSE: Naturally occurring dysfunction in NaV channels results in complex disorders such as chronic pain, making these channels an attractive target for new therapies. In the pursuit of novel NaV modulators, we investigated spider venoms for new inhibitors of NaV channels. EXPERIMENTAL APPROACH: We used high-throughput screens to identify a NaV modulator in venom of the spider Davus fasciatus. Further characterization of this venom peptide was undertaken using fluorescent and electrophysiological assays, molecular modeling and a rodent pain model...
May 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28541485/histologically-defined-intratumoral-sequencing-uncovers-evolutionary-cues-into-conserved-molecular-events-driving-gliomagenesis
#6
Antony Prabhu, Pravin Kesarwani, Shiva Kant, Stewart F Graham, Prakash Chinnaiyan
BACKGROUND: Glioblastoma represents an archetypal example of a heterogeneous malignancy. To understand the diverse molecular consequences of this complex tumor ecology, we analyzed RNA-seq data generated from commonly identified intra-tumoral structures in glioblastoma enriched using laser capture microdissection. METHODS: Raw gene-level fragments per kilobase of transcript per million reads mapped (FPKM) values and the associated clinical data were acquired from the publically available Ivy GAP database and analyzed using MetaboAnalyst (v...
May 25, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28541380/a-fully-bayesian-latent-variable-model-for-integrative-clustering-analysis-of-multi-type-omics-data
#7
Qianxing Mo, Ronglai Shen, Cui Guo, Marina Vannucci, Keith S Chan, Susan G Hilsenbeck
Identification of clinically relevant tumor subtypes and omics signatures is an important task in cancer translational research for precision medicine. Large-scale genomic profiling studies such as The Cancer Genome Atlas (TCGA) Research Network have generated vast amounts of genomic, transcriptomic, epigenomic, and proteomic data. While these studies have provided great resources for researchers to discover clinically relevant tumor subtypes and driver molecular alterations, there are few computationally efficient methods and tools for integrative clustering analysis of these multi-type omics data...
May 24, 2017: Biostatistics
https://www.readbyqxmd.com/read/28540766/hiv-1-full-genome-phylogenetics-of-generalized-epidemics-in-sub-saharan-africa-impact-of-missing-nucleotide-characters-in-next-generation-sequences
#8
Oliver Ratmann, Chris Wymant, Caroline Colijn, Siva Danaviah, M Essex, Simon D W Frost, Astrid Gall, Simani Gaiseitsiwe, Mary Grabowski, Ronald Gray, Stephane Guindon, Arndt von Haeseler, Pontiano Kaleebu, Michelle Kendall, Alexey Kozlov, Justen Manasa, Bui Quang Minh, Sikhulile Moyo, Vladimir Novitsky, Rebecca Nsubuga, Sureshnee Pillay, Thomas C Quinn, David Serwadda, Deogratius Ssemwanga, Alexandros Stamatakis, Jana Trifinopoulos, Maria Wawer, Andrew Leigh Brown, Tulio de Oliveira, Paul Kellam, Deenan Pillay, Christophe Fraser
To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai...
May 25, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28540508/molecular-characterization-of-blastocystis-sp-in-captive-wild-animals-in-qinling-mountains
#9
G H Zhao, X F Hu, T L Liu, R S Hu, Z Q Yu, W B Yang, Y L Wu, S K Yu, J K Song
Blastocystis is one common protist inhabiting in gastrointestinal tracts of animals and humans. Examining the subtypes has important implications for assessing the zoonotic potential of Blastocystis and intestinal health of hosts. In the present study, a total of 497 fecal samples collected from 37 wild animal species in Qinling Mountains were investigated for the presence and subtypes of Blastocystis. Of them, 200 (40.2%) were positive for Blastocystis and 13 subtypes were found, including eight known subtypes (STs1-3, 5, 10, 12-14) and five possible novel subtypes (temporarily named as STs18-22), with ST10 as the predominate subtype and the subtype ST5 was detected in an ostrich for the first time...
May 24, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28539169/effectiveness-of-four-inflammatory-markers-in-predicting-prognosis-in-2374-women-with-breast-cancer
#10
Bárbara Reis Wariss, Karen de Souza Abrahão, Suzana Sales de Aguiar, Anke Bergmann, Luiz Claudio Santos Thuler
OBJECTIVE: To analyze the association between four biomarkers and overall survival in patients with breast cancer (BC). METHODOLOGY: This cohort study had a sample of 2374 women over the age of 18, diagnosed and treated in a single reference center for BC in Brazil, during the year 2008-2009. The following pretreatment indices were analyzed: neutrophil-lymphocyte ratio (NLR), a derived neutrophil-lymphocyte ratio (dNLR), absolute neutrophil count (ANC) and platelet-lymphocyte ratio (PLR)...
July 2017: Maturitas
https://www.readbyqxmd.com/read/28539123/multilevel-genomics-of-colorectal-cancers-with-microsatellite-instability-clinical-impact-of-jak1-mutations-and-consensus-molecular-subtype-1
#11
Anita Sveen, Bjarne Johannessen, Torstein Tengs, Stine A Danielsen, Ina A Eilertsen, Guro E Lind, Kaja C G Berg, Edward Leithe, Leonardo A Meza-Zepeda, Enric Domingo, Ola Myklebost, David Kerr, Ian Tomlinson, Arild Nesbakken, Rolf I Skotheim, Ragnhild A Lothe
BACKGROUND: Approximately 15% of primary colorectal cancers have DNA mismatch repair deficiency, causing a complex genome with thousands of small mutations-the microsatellite instability (MSI) phenotype. We investigated molecular heterogeneity and tumor immunogenicity in relation to clinical endpoints within this distinct subtype of colorectal cancers. METHODS: A total of 333 primary MSI+ colorectal tumors from multiple cohorts were analyzed by multilevel genomics and computational modeling-including mutation profiling, clonality modeling, and neoantigen prediction in a subset of the tumors, as well as gene expression profiling for consensus molecular subtypes (CMS) and immune cell infiltration...
May 24, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28537543/molecular-epidemiology-of-hepatitis-b-virus-infection-in-tanzania
#12
Joseph C Forbi, Michael Dillon, Michael A Purdy, Bakary S Drammeh, Alexandra Tejada-Strop, Daniel McGovern, Guo-Liang Xia, Yulin Lin, Lilia M Ganova-Raeva, David S Campo, Hong Thai, Gilberto Vaughan, Dunstan Haule, Regina P Kutaga, Sridhar V Basavaraju, Saleem Kamili, Yury E Khudyakov
Despite the significant public health problems associated with hepatitis B virus (HBV) in sub-Saharan Africa, many countries in this region do not have systematic HBV surveillance or genetic information on HBV circulating locally. Here, we report on the genetic characterization of 772 HBV strains from Tanzania. Phylogenetic analysis of the S-gene sequences showed prevalence of HBV genotype A (HBV/A, n=671, 86.9 %), followed by genotypes D (HBV/D, n=95, 12.3 %) and E (HBV/E, n=6, 0.8 %). All HBV/A sequences were further classified into subtype A1, while the HBV/D sequences were assigned to a new cluster...
May 25, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28536141/melk-and-ezh2-cooperate-to-regulate-medulloblastoma-cancer-stem-like-cell-proliferation-and-differentiation
#13
Hailong Liu, Qianwen Sun, Youliang Sun, Junping Zhang, Hongyu Yuan, Shuhuan Pang, Xueling Qi, Haoran Wang, Mingshan Zhang, Honwei Zhang, Chunjiang Yu, Chunyu Gu
Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported that more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stem-like cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog (SHH)-subtype medulloblastoma...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28535939/gene-expression-profiling-of-large-cell-lung-cancer-links-transcriptional-phenotypes-to-the-new-histological-who2015-classification
#14
Anna Karlsson, Hans Brunnström, Patrick Micke, Srinivas Veerla, Johanna Mattsson, Linnea La Fleur, Johan Botling, Mats Jönsson, Christel Reuterswärd, Maria Planck, Johan Staaf
INTRODUCTION: Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes a small proportion of non-small cell lung cancer (NSCLC). The WHO2015 classification guidelines changed the definition of the debated histological subtype LC to be based on immunomarkers for adenocarcinoma and squamous cancer. We sought to determine if these new guidelines translate also to the transcriptional landscape of lung cancer, and LC specifically. METHODS: Gene expression profiling was performed using Illumina V4 HT12 microarrays on 159 cases (comprising all histological subtypes including 10 WHO2015 LC and 14 LCNEC tumors), with complimentary mutational and IHC data...
May 20, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28535188/molecular-heterogeneity-at-the-network-level-high-dimensional-testing-clustering-and-a-tcga-case-study
#15
Nicolas Städler, Frank Dondelinger, Steven M Hill, Rehan Akbani, Yiling Lu, Gordon B Mills, Sach Mukherjee
Motivation: Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging. Furthermore, since network differences could provide important and biologically interpretable information to identify molecular subgroups, there is a need to consider the unsupervised task of learning subgroups and networks that define them...
May 23, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28534358/prognostic-implications-of-the-intrinsic-molecular-subtypes-in-male-breast-cancer
#16
Abdeljaoued Syrine, Bettaieb Lhem, Nasri Meher, Adouni Olfa, Goucha Aida, Bouzaiene Hatem, Boussen Hamouda, Rahal Khaled, Gamoudi Amor
PURPOSE: Intrinsic molecular subtyping has been widely used in female breast cancer, and it has proven its significance. In this article, we aimed to study the intrinsic subtypes of male breast cancer (MBC) in correlation with clinicopathological features. METHODS: We retrospectively identified 130 MBC cases from 2004 to 2013. Intrinsic molecular subtypes were determined by immunohistochemistry (IHC). RESULTS: From a total of 130 MBC cases, 45...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28534222/identification-of-innate-lymphoid-cells-in-single-cell-rna-seq-data
#17
Madeleine Suffiotti, Santiago J Carmona, Camilla Jandus, David Gfeller
Innate lymphoid cells (ILCs) consist of natural killer (NK) cells and non-cytotoxic ILCs that are broadly classified into ILC1, ILC2, and ILC3 subtypes. These cells recently emerged as important early effectors of innate immunity for their roles in tissue homeostasis and inflammation. Over the last few years, ILCs have been extensively studied in mouse and human at the functional and molecular level, including gene expression profiling. However, sorting ILCs with flow cytometry for gene expression analysis is a delicate and time-consuming process...
May 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28534152/cerebrospinal-fluid-dissemination-of-high-grade-gliomas-following-boron-neutron-capture-therapy-occurs-more-frequently-in-the-small-cell-subtype-of-idh1-r132h-mutation-negative-glioblastoma
#18
Natsuko Kondo, Rolf F Barth, Shin-Ichi Miyatake, Shinji Kawabata, Minoru Suzuki, Koji Ono, Norman L Lehman
We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT...
May 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28532995/histological-subtypes-of-hepatocellular-carcinoma-are-related-to-gene-mutations-and-molecular-tumour-classification
#19
Julien Calderaro, Gabrielle Couchy, Sandrine Imbeaud, Giuliana Amaddeo, Eric Letouzé, Jean-Frédéric Blanc, Christophe Laurent, Yacine Hajji, Daniel Azoulay, Paulette Bioulac-Sage, Jean-Charles Nault, Jessica Zucman-Rossi
BACKGROUND AND AIMS: Our increasing understanding of hepatocellular carcinoma (HCC) biology holds promise for personalized care, however its translation into clinical practice requires a precise knowledge of its relationship to tumour phenotype. METHODS: We aimed at investigating molecular-phenotypic correlations in a large series of HCC. To this purpose, 343 surgically resected HCC were investigated by pathological review, immunohistochemistry, gene expression profiling and sequencing...
May 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28532485/multidimensional-scaling-of-diffuse-gliomas-application-to-the-2016-world-health-organization-classification-system-with-prognostically-relevant-molecular-subtype-discovery
#20
Patrick J Cimino, Michael Zager, Lisa McFerrin, Hans-Georg Wirsching, Hamid Bolouri, Bettina Hentschel, Andreas von Deimling, David Jones, Guido Reifenberger, Michael Weller, Eric C Holland
Recent updating of the World Health Organization (WHO) classification of central nervous system (CNS) tumors in 2016 demonstrates the first organized effort to restructure brain tumor classification by incorporating histomorphologic features with recurrent molecular alterations. Revised CNS tumor diagnostic criteria also attempt to reduce interobserver variability of histological interpretation and provide more accurate stratification related to clinical outcome. As an example, diffuse gliomas (WHO grades II-IV) are now molecularly stratified based upon isocitrate dehydrogenase 1 or 2 (IDH) mutational status, with gliomas of WHO grades II and III being substratified according to 1p/19q codeletion status...
May 22, 2017: Acta Neuropathologica Communications
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