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https://www.readbyqxmd.com/read/28324890/regulation-of-itga3-by-the-dual-stranded-microrna-199-family-as-a-potential-prognostic-marker-in-bladder-cancer
#1
Takashi Sakaguchi, Hirofumi Yoshino, Masaya Yonemori, Kazutaka Miyamoto, Satoshi Sugita, Ryosuke Matsushita, Toshihiko Itesako, Shuichi Tatarano, Masayuki Nakagawa, Hideki Enokida
BACKGROUND: Based on the microRNA (miRNA) signature of bladder cancer (BC) by deep sequencing, we recently found that several double-stranded mature miRNAs derived from the same pre-miRNAs were sufficiently expressed and acted as tumour suppressors by regulating common target genes in BC. Our deep-sequencing signature of BC showed that all miR-199 family members (miR-199a-3p/-5p and miR-199b-3p/-5p) were also downregulated. We hypothesised that these miRNAs may function as tumour suppressors by regulating common target genes...
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28319171/a-reported-20-gene-expression-signature-to-predict-lymph-node-positive-disease-at-radical-cystectomy-for-muscle-invasive-bladder-cancer-is-clinically-not-applicable
#2
Kim E M van Kessel, Harmen J G van de Werken, Irene Lurkin, Angelique C J Ziel-van der Made, Ellen C Zwarthoff, Joost L Boormans
BACKGROUND: Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that predicted lymph node-positive disease at radical cystectomy in clinically node-negative MIBC patients, which would be a justification for upfront chemotherapy...
2017: PloS One
https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#3
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28314692/identification-of-an-atypical-etiological-head-and-neck-squamous-carcinoma-subtype-featuring-the-cpg-island-methylator-phenotype
#4
K Brennan, J L Koenig, A J Gentles, J B Sunwoo, O Gevaert
Head and neck squamous cell carcinoma (HNSCC) is broadly classified into HNSCC associated with human papilloma virus (HPV) infection, and HPV negative HNSCC, which is typically smoking-related. A subset of HPV negative HNSCCs occur in patients without smoking history, however, and these etiologically 'atypical' HNSCCs disproportionately occur in the oral cavity, and in female patients, suggesting a distinct etiology. To investigate the determinants of clinical and molecular heterogeneity, we performed unsupervised clustering to classify 528 HNSCC patients from The Cancer Genome Atlas (TCGA) into putative intrinsic subtypes based on their profiles of epigenetically (DNA methylation) deregulated genes...
March 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28314268/clinical-significance-of-fancd2-gene-expression-and-its-association-with-tumor-progression-in-hepatocellular-carcinoma
#5
Hisateru Komatsu, Takaaki Masuda, Tomohiro Iguchi, Sho Nambara, Kuniaki Sato, Quingjang Hu, Hidenari Hirata, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori
BACKGROUND/AIM: Fanconi anemia complementation group D2 (FANCD2) gene is vitally involved in DNA damage responses. We investigated the clinical significance of FANCD2 expression in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: FANCD2 mRNA expression of resected HCC tissues was assessed in two HCC cohorts; Our cases (n=111), and The Cancer Genome Atlas (TCGA; n=371). Gene set enrichment analysis (GSEA) was conducted using the TCGA dataset. Proliferation and invasion assays were performed using siRNAs, and the effect of inhibition of the mechanistic target of rapamycin (mTOR) pathway was evaluated...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28304380/comprehensive-analysis-of-the-cancer-genome-atlas-reveals-a-unique-gene-and-non-coding-rna-signature-of-fibrolamellar-carcinoma
#6
Timothy A Dinh, Eva C M Vitucci, Eliane Wauthier, Rondell P Graham, Wendy A Pitman, Tsunekazu Oikawa, Mengjie Chen, Grace O Silva, Kevin G Greene, Michael S Torbenson, Lola M Reid, Praveen Sethupathy
Fibrolamellar carcinoma (FLC) is a unique liver cancer primarily affecting young adults and characterized by a fusion event between DNAJB1 and PRKACA. By analyzing RNA-sequencing data from The Cancer Genome Atlas (TCGA) for >9,100 tumors across ~30 cancer types, we show that the DNAJB1-PRKACA fusion is specific to FLCs. We demonstrate that FLC tumors (n = 6) exhibit distinct messenger RNA (mRNA) and long intergenic non-coding RNA (lincRNA) profiles compared to hepatocellular carcinoma (n = 263) and cholangiocarcinoma (n = 36), the two most common liver cancers...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296140/inhibitors-of-stat3-%C3%AE-catenin-and-igf-1r-sensitize%C3%A2-mouse-pik3ca%C3%A2-mutant%C3%A2-breast-cancer-to-pi3k-inhibitors
#7
Vanessa F Merino, Soonweng Cho, Xiaohui Liang, Sunju Park, Kideok Jin, Qian Chen, Duojia Pan, Cynthia A Zahnow, Alan R Rein, Saraswati Sukumar
Although mutations in the phosphoinositide 3-kinase-catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic mouse models expressing the human PIK3CA-H1047R and the -E545K hotspot mutant genes in the mammary gland and evaluated their effects on development and tumor formation. Molecular analysis identified pathways altered in these mutant tumors, which were also targeted in multiple cells lines derived from the PIK3CA tumors...
March 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28295365/comparative-transcriptome-analysis-of-isogenic-cell-line-models-and-primary-cancers-links-cic-loss-to-activation-of-the-mapk-signalling-cascade
#8
Veronique G LeBlanc, Marlo Firme, Jungeun Song, Susanna Y Chan, Min Hye Lee, Stephen Yip, Suganthi Chittaranjan, Marco A Marra
CIC encodes a transcriptional repressor whose disrupted activity appears to be involved in several cancer types, including Type I low-grade gliomas (LGGs) and stomach adenocarcinomas (STADs). To explore human CIC's transcriptional network in an isogenic background, we developed novel isogenic CIC knockout cell lines as model systems and used these in transcriptome analyses to study the consequences of CIC loss. We also compared our results to analyses of transcriptome data from TCGA for Type I LGGs and STADs...
March 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28291637/is-the-cancer-genome-atlas-tcga-bladder-cancer-cohort-representative-of-invasive-bladder-cancer
#9
Roland Seiler, Peter C Black, George Thalmann, Arnulf Stenzl, Tilman Todenhöfer
PURPOSE: The Cancer Genome Atlas (TCGA) Research Consortium has conducted a comprehensive molecular characterization of invasive bladder cancer (BCa). This open-access dataset has become the critical reference for studying biomarkers and mechanisms of disease in BCa. In order for this data to be considered representative, and to allow comparisons of markers between cohorts, clinicopathologic characteristics of this cohort need to conform to those established for this disease state. The aim of this study was to critically evaluate clinicopathologic characteristics and outcomes of the TCGA BCa cohort in comparison with published cystectomy series...
March 10, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28289712/rcan1-4-is-a-thyroid-cancer-growth-and-metastasis-suppressor
#10
Chaojie Wang, Motoyasu Saji, Steven E Justiniano, Adlina Mohd Yusof, Xiaoli Zhang, Lianbo Yu, Soledad Fernández, Paul Wakely, Krista La Perle, Hiroshi Nakanishi, Neal Pohlman, Matthew D Ringel
Metastasis suppressors are key regulators of tumor growth, invasion, and metastases. Loss of metastasis suppressors has been associated with aggressive tumor behaviors and metastatic progression. We previously showed that regulator of calcineurin 1, isoform 4 (RCAN1-4) was upregulated by the KiSS1 metastatic suppression pathway and could inhibit cell motility when overexpressed in cancer cells. To test the effects of endogenous RCAN1-4 loss on thyroid cancer in vivo, we developed RCAN1-4 knockdown stable cells...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288905/bioinformatic-approaches-to-interrogating-vitamin-d-receptor-signaling
#11
Moray J Campbell
Bioinformatics applies unbiased approaches to develop statistically-robust insight into health and disease. At the global, or "20,000 foot" view bioinformatic analyses of vitamin D receptor (NR1I1/VDR) signaling can measure where the VDR gene or protein exerts a genome-wide significant impact on biology; VDR is significantly implicated in bone biology and immune systems, but not in cancer. With a more VDR-centric, or "2000 foot" view, bioinformatic approaches can interrogate events downstream of VDR activity...
March 10, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28287129/akt1-and-akt2-isoforms-play-distinct-roles-during-breast-cancer-progression-through-the-regulation-of-specific-downstream-proteins
#12
Marina Riggio, María C Perrone, María L Polo, María J Rodriguez, María May, Martín Abba, Claudia Lanari, Virginia Novaro
The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286086/hyper-methylation-of-the-upstream-cpg-island-shore-is-a-likely-mechanism-of-gper1-silencing-in-breast-cancer-cells
#13
Mohan C Manjegowda, Paridhi Singhal Gupta, Anil M Limaye
GPER1, also known as GPR30, is a novel seven-transmembrane G-protein coupled estrogen receptor that mediates both short-term (non-genomic) and long-term (genomic) effects of estrogen in target cells and tissues. A substantial body of work over the last two decades has highlighted its therapeutic or prognostic utility. However, the clinical data on the expression of GPER1 in breast tissue is ambiguous. Analysis of TCGA RNAseq data revealed significantly lower mean expression of GPER1 mRNA in primary breast tumors compared to that in normal breast tissues...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28281325/b-raf-mutations-are-associated-with-increased-iron-regulatory-protein-2-expression-in-colorectal-tumourigenesis
#14
Richard D Horniblow, Matthew Bedford, Robert Hollingworth, Sarah Evans, Emily Sutton, Neeraj Lal, Andrew Beggs, Tariq H Iqbal, Chris Tselepis
A role for iron in carcinogenesis is supported by evidence that iron metabolism proteins are modulated in cancer progression. To date however, the expression of IRP2 (Iron Regulatory Protein-2), which is known to regulate several iron metabolism proteins, has not been assessed in colorectal cancer. Expression of IRP2 was assessed by qRT-PCR and immunohistochemistry in human colorectal cancer tissue. By interrogating The Cancer Genome Atlas (TCGA) database, expression of IRP2 and transferrin receptor-1 (TfR1) was assessed relative to common mutations that are known to occur in cancer...
March 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28279784/emerging-role-of-dubs-in-tumor-metastasis-and-apoptosis-therapeutic-implication
#15
REVIEW
Mingjing He, Zhuan Zhou, George Wu, Qianming Chen, Yong Wan
Malfunction of ubiquitin-proteasome system is tightly linked to tumor formation and tumor metastasis. Targeting the ubiquitin-pathway provides a new strategy for anti-cancer therapy. Despite the parts played by ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in governing the multiple steps of the metastatic cascade, including local invasion, dissemination, and eventual colonization of the tumor to distant organs. Both deregulated ubiquitination and deubiquitination could lead to dysregulation of various critical events and pathways such as apoptosis and epithelial-mesenchymal transition (EMT)...
March 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28278225/identification-of-endometrial-cancer-methylation-features-using-combined-methylation-analysis-methods
#16
Michael P Trimarchi, Pearlly Yan, Joanna Groden, Ralf Bundschuh, Paul J Goodfellow
BACKGROUND: DNA methylation is a stable epigenetic mark that is frequently altered in tumors. DNA methylation features are attractive biomarkers for disease states given the stability of DNA methylation in living cells and in biologic specimens typically available for analysis. Widespread accumulation of methylation in regulatory elements in some cancers (specifically the CpG island methylator phenotype, CIMP) can play an important role in tumorigenesis. High resolution assessment of CIMP for the entire genome, however, remains cost prohibitive and requires quantities of DNA not available for many tissue samples of interest...
2017: PloS One
https://www.readbyqxmd.com/read/28278055/comparative-analyses-identify-molecular-signature-of-mri-classified-svz-associated-glioblastoma
#17
Chin-Hsing Annie Lin, Christopher T Rhodes, ChenWei Lin, Joanna J Phillips, Mitchel S Berger
Glioblastoma (GBM) is a highly aggressive brain cancer with limited therapeutic options. While efforts to identify genes responsible for GBM have revealed mutations and aberrant gene expression associated with distinct types of GBM, patients with GBM are often diagnosed and classified based on MRI features. Therefore, we seek to identify molecular representatives in parallel with MRI classification for group I and group II primary GBM associated with the subventricular zone (SVZ). As group I and II GBM contain stem-like signature, we compared gene expression profiles between these 2 groups of primary GBM and endogenous neural stem progenitor cells to reveal dysregulation of cell cycle, chromatin status, cellular morphogenesis, and signaling pathways in these 2 types of MRI-classified GBM...
February 22, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28277540/p53-loss-of-heterozygosity-is-a-necessary-prerequisite-for-mutant-p53-stabilization-and-gain-of-function-in-vivo
#18
Evguenia M Alexandrova, Safia A Mirza, Sulan Xu, Ramona Schulz-Heddergott, Natalia D Marchenko, Ute M Moll
Missense mutations in TP53 comprise >75% of all p53 alterations in cancer, resulting in highly stabilized mutant p53 proteins that not only lose their tumor-suppressor activity, but often acquire oncogenic gain-of-functions (GOFs). GOF manifests itself in accelerated tumor onset, increased metastasis, increased drug resistance and shortened survival in patients and mice. A known prerequisite for GOF is mutant p53 protein stabilization, which itself is linked to aberrant protein conformation. However, additional determinants for mutant p53 stabilization likely exist...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28276478/b-myb-induces-apobec3b-expression-leading-to-somatic-mutation-in-multiple-cancers
#19
Wen-Cheng Chou, Wei-Ting Chen, Chia-Ni Hsiung, Ling-Yueh Hu, Jyh-Cherng Yu, Huan-Ming Hsu, Chen-Yang Shen
The key signature of cancer genomes is the accumulation of DNA mutations, the most abundant of which is the cytosine-to-thymine (C-to-T) transition that results from cytosine deamination. Analysis of The Cancer Genome Atlas (TCGA) database has demonstrated that this transition is caused mainly by upregulation of the cytosine deaminase APOBEC3B (A3B), but the mechanism has not been completely characterized. We found that B-Myb (encoded by MYBL2) binds the A3B promoter, causing transactivation, and this is responsible for the C-to-T transitions and DNA hypermutation in breast cancer cells...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271066/visual-display-of-5p-arm-and-3p-arm-mirna-expression-with-a-mobile-application
#20
Chao-Yu Pan, Wei-Ting Kuo, Chien-Yuan Chiu, Wen-Chang Lin
MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information...
2017: BioMed Research International
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