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Julia Drube, Thomas Ernst, Markus Pfirrmann, Benadict Vincent Albert, Sebastian Drube, Daniela Reich, Anne Kresinsky, Kathrin Halfter, Claudio Sorio, Christian Fabisch, Andreas Hochhaus, Frank-D Böhmer
The introduction of second-generation tyrosine kinase inhibitors (TKIs) targeting the protein-tyrosine kinase (PTK) BCR-ABL1 has improved treatment response in chronic myeloid leukemia (CML). However, in some patients response still remains suboptimal. Protein-tyrosine phosphatases (PTPs) are natural counter-actors of PTK activity and can affect TKI sensitivity, but the impact of PTPs on treatment response to second-generation TKIs is unknown. We assessed the mRNA expression level of 38 PTPs in 66 newly diagnosed CML patients and analyzed the potential relation with treatment outcome after 9 months of nilotinib medication...
February 6, 2018: Oncotarget
Gabriel Santpere, Ana Alcaráz-Sanabria, Verónica Corrales-Sánchez, Atanasio Pandiella, Balázs Győrffy, Alberto Ocaña
In breast cancer, it is unclear the functional modifications at a transcriptomic level that are associated with the evolution from epithelial cells and ductal carcinoma in situ (DCIS) to basal-like tumors. By applying weighted gene co-expression network analysis (WGCNA), we identified 17 gene co-expression modules in normal, DCIS and basal-like tumor samples. We then correlated the expression pattern of these gene modules with disease progression from normal to basal-like tumours and found eight modules exhibiting a high and statistically significant correlation...
January 2, 2018: Oncotarget
Patricia Johansson, Ludger Klein-Hitpass, Axel Choidas, Peter Habenberger, Bijan Mahboubi, Baek Kim, Anke Bergmann, René Scholtysik, Martina Brauser, Anna Lollies, Reiner Siebert, Thorsten Zenz, Ulrich Dührsen, Ralf Küppers, Jan Dürig
T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. Besides characteristic chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT pathway members, and epigenetic regulators. We here performed a targeted mutation analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations were identified in 30 of the 40 genes, 18 being recurrently mutated...
January 19, 2018: Blood Cancer Journal
Erlin Song, Wenting Song, Minghua Ren, Li Xing, Wenjun Ni, Yongxiang Li, Mancheng Gong, Mingbo Zhao, Xin Ma, Xu Zhang, Ruihua An
Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with high mortality. However, the molecular pathogenesis of ccRCC remains unclear and effective biomarkers for daily practice are still limited. Thus, we aimed to identify the potential crucial genes and pathways associated with carcinogenesis of ccRCC and further analyze the molecular mechanisms implicated in tumorigenesis. In the present study, expression profiles GSE 66270, GSE 53757, GSE 36895 and GSE 76351 were downloaded from GEO database, including 244 matched primary and adjacent normal tissues, furthermore, the level 3 RNAseq dataset (RNAseqV2 RSEM) of KIRC was also downloaded from The Cancer Genome Atlas (TCGA), which consist of 529 ccRCC tumors and 72 normal tissues...
December 11, 2017: Journal of Cellular Biochemistry
I Tycová, P Hrubá, D Maixnerová, E Girmanová, P Mrázová, L Straňavová, R Zachoval, M Merta, J Slatinská, M Kollár, E Honsová, V Tesař, O Viklický
The aim of the study was to characterize by molecular profiling two glomerular diseases: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) and to identify potential molecular markers of IgAN and FSGS progression. The expressions of 90 immune-related genes were compared in biopsies of patients with IgAN (n=33), FSGS (n=17) and in controls (n=11) using RT-qPCR. To identify markers of disease progression, gene expression was compared between progressors and non-progressors in 1 year follow-up...
November 10, 2017: Physiological Research
Piotr Andrzej Sass, Michał Dąbrowski, Agata Charzyńska, Paweł Sachadyn
BACKGROUND: A vast amount of microarray data on transcriptomic response to injury has been collected so far. We designed the analysis in order to identify the genes displaying significant changes in expression after wounding in different organisms and tissues. This meta-analysis is the first study to compare gene expression profiles in response to wounding in as different tissues as heart, liver, skin, bones, and spinal cord, and species, including rat, mouse and human. RESULTS: We collected available microarray transcriptomic profiles obtained from different tissue injury experiments and selected the genes showing a minimum twofold change in expression in response to wounding in prevailing number of experiments for each of five wound healing stages we distinguished: haemostasis & early inflammation, inflammation, early repair, late repair and remodelling...
November 7, 2017: BMC Genomics
Ayako Takuma, Arata Abe, Yoshikazu Saito, Chikako Nito, Masayuki Ueda, Yoshiro Ishimaru, Hideki Harada, Keiko Abe, Kazumi Kimura, Tomiko Asakura
Given the abundance of stroke patients and deaths from stroke worldwide, many studies concerning the aftermath of stroke are being carried out. To reveal the precise effect of ischemic infarction, we conducted a comprehensive gene expression analysis. Alongside a middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model, we used a group undergoing sham surgery for comparison, which was the same as MCAO surgery but without blood vessel occlusion. Subsequently, infarction of the brains of MCAO-treated rats occurred, but did not occur in the sham-treated rats...
November 5, 2017: International Journal of Molecular Sciences
S A Zamorina, L S Litvinova, K A Yurova, O G Khaziakhmatova, V P Timganova, M S Bochkova, P V Khramtsov, M B Rayev
The role of human chorionic gonadotropin (hCG) in the regulation of molecular genetics factors determining the functional activity of human naïve and memory T cells in vitro was studied. It was found that hCG (10 and 100IU/ml) inhibited CD28 and CD25 expression on the naïve T cells (CD45RA+) and CD25 expression on the memory T cells (CD45R0+). hCG didn't affect the CD71 proliferation marker expression in total. Nevertheless, hCG reduced the percentage of proliferating memory T cells with simultaneous suppression of CD71 expression on proliferating CD45R0+cells...
October 28, 2017: International Immunopharmacology
Maria I Zervou, Despoina G Dimopoulou, Elias Eliopoulos, Maria Trachana, Polyxeni Pratsidou-Gkertsi, Athena Andreou, Prodromos Sidiropoulos, Demetrios A Spandidos, Alexandros Garyfallos, George N Goulielmos
Juvenile idiopathic arthritis (JIA) is an autoimmune disease that is characterized by persistent chronic arthritis and affected by genetic and environmental factors. Different genetic variations have been reported as risk factors for JIA. However, given that many results could not be replicated in individuals of different ancestral origin, it was assumed that heterogeneous genetic factors are involved in this disease. In the present study, we analyzed three single nucleotide polymorphisms (SNPs), namely PTPRC (rs10919563), TYK2 (rs34536443) and PRKCQ (rs4750316), which were found to be associated with JIA in previous studies...
December 2017: Molecular Medicine Reports
Kondreddy Eswar Reddy, Woong Lee, Jin Young Jeong, Yookyung Lee, Hyun-Jeong Lee, Min Seok Kim, Dong-Woon Kim, Dongjo Yu, Ara Cho, Young Kyoon Oh, Sung Dae Lee
Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0...
September 18, 2017: Asian-Australasian Journal of Animal Sciences
Johannes Landskron, Sigrid M Kraggerud, Elisabeth Wik, Anne Dørum, Merete Bjørnslett, Espen Melum, Øystein Helland, Line Bjørge, Ragnhild A Lothe, Helga B Salvesen, Kjetil Taskén
The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon's differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive...
2017: PloS One
Songtao Chu, Haipeng Wang, Miao Yu
BACKGROUND: This study aimed to identify the potential molecular network associated with colon cancer metastasis. METHODS: A gene expression profile dataset (GSE40367) downloaded from Gene Expression Omnibus was used to identify and compare differentially expressed genes (DEGs) between primary colon adenocarcinoma tissues and matched tissue samples of liver metastases of colon adenocarcinoma. After the functional analysis of the DEGs, their protein-protein interactions (PPIs) were analyzed, and the transcription factors (TFs) and microRNAs (miRNAs) that regulated these DEGs were predicted...
June 19, 2017: World Journal of Surgical Oncology
Kathleen M Schieffer, Christine S Choi, Scott Emrich, Leonard Harris, Sue Deiling, Dipti M Karamchandani, Anna Salzberg, Yuka I Kawasawa, Gregory S Yochum, Walter A Koltun
Individuals with diverticula or outpouchings of the colonic mucosa and submucosa through the colonic wall have diverticulosis, which is usually asymptomatic. In 10-25% of individuals, the diverticula become inflamed, resulting in diverticulitis. Very little is known about the pathophysiology or gene regulatory pathways involved in the development of diverticulitis. To identify these pathways, we deep sequenced RNAs isolated from full-thickness sections of sigmoid colon from diverticulitis patients and control individuals...
September 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
S Bek, A B Bojesen, J V Nielsen, J Sode, S Bank, U Vogel, V Andersen
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis...
October 2017: Pharmacogenomics Journal
Katarzyna Iżykowska, Grzegorz K Przybylski, Claudia Gand, Floriane C Braun, Piotr Grabarczyk, Andreas W Kuss, Karolina Olek-Hrab, Armando N Bastidas Torres, Maarten H Vermeer, Willem H Zoutman, Cornelis P Tensen, Christian A Schmidt
Sézary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma variant. Molecular pathogenesis of SS is still unclear despite many studies on genetic alterations, gene expression and epigenetic regulations. Through whole genome and transcriptome next generation sequencing nine Sézary syndrome patients were analyzed in terms of copy number variations and rearrangements affecting gene expression. Recurrent copy number variations were detected within 8q (MYC, TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1), but no recurrent rearrangements were identified...
June 13, 2017: Oncotarget
Gabriel N Teku, Mauno Vihinen
Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly rare disorders that affect the immune system. T-cell deficiencies account for about one-tenth of PIDs, most of them being monogenic. Apart from genetic and clinical information, lots of other data are available for PID proteins and genes, including functions and interactions. Thus, it is possible to perform systems biology studies on the effects of PIDs on T-cell physiology and response. To achieve this, we reconstructed a T-cell network model based on literature mining and TPPIN, a previously published core T-cell network, and performed semi-quantitative dynamic network simulations on both normal and T-cell PID failure modes...
2017: PloS One
Keisuke Kosumi, Yohei Masugi, Juhong Yang, Zhi Rong Qian, Sun A Kim, Wanwan Li, Yan Shi, Annacarolina da Silva, Tsuyoshi Hamada, Li Liu, Mancang Gu, Tyler S Twombly, Yin Cao, David A Barbie, Katsuhiko Nosho, Hideo Baba, Wendy S Garrett, Jeffery A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Shuji Ogino, Reiko Nishihara
Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study...
2017: Oncoimmunology
R Doug Wagner, Shemedia J Johnson
BACKGROUND: Salmonella enterica infections often exhibit a form of immune evasion. We previously observed that probiotic bacteria could prevent inhibition of lymphoproliferation and apoptosis responses of T cells associated with S. enterica infections in orally challenged mice. RESULTS: In this study, changes in expression of genes related to lymphocyte activation in mucosa-associated lymphoid tissues (MALT) of mice orally infected with S. enterica with and without treatment with probiotic bacteria were evaluated...
March 29, 2017: BMC Microbiology
Sole Gatto, Miriam Gagliardi, Monica Franzese, Sylwia Leppert, Mariarosaria Papa, Marco Cammisa, Giacomo Grillo, Guillame Velasco, Claire Francastel, Shir Toubiana, Maurizio D'Esposito, Claudia Angelini, Maria R Matarazzo
Hypomorphic mutations in DNA-methyltransferase DNMT3B cause majority of the rare disorder Immunodeficiency, Centromere instability and Facial anomalies syndrome cases (ICF1). By unspecified mechanisms, mutant-DNMT3B interferes with lymphoid-specific pathways resulting in immune response defects. Interestingly, recent findings report that DNMT3B shapes intragenic CpG-methylation of highly-transcribed genes. However, how the DNMT3B-dependent epigenetic network modulates transcription and whether ICF1-specific mutations impair this process remains unknown...
June 2, 2017: Nucleic Acids Research
Yongfei Hu, Yan Huang, Ying Yi, Hongwei Wang, Bing Liu, Jia Yu, Dong Wang
Accumulating evidence has demonstrated that macroautophagy/autophagy plays an essential role in self-renewal and differentiation in embryonic hematopoiesis. Here, according to the RNA sequencing data sets of 5 population cells related to hematopoietic stem cell (HSC) formation during mouse embryogenesis (endothelial cells, PTPRC/CD45- and PTPRC/CD45+ pre-HSCs in the E11 aorta-gonad-mesonephros (AGM) region, mature HSCs in E12 and E14 fetal liver), we explored the dynamic expression of mouse autophagy-related genes in this course at the single-cell level...
April 3, 2017: Autophagy
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