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https://www.readbyqxmd.com/read/28427185/transcriptional-landscape-of-human-cancers
#1
Mengyuan Li, Qingrong Sun, Xiaosheng Wang
The homogeneity and heterogeneity in somatic mutations, copy number alterations and methylation across different cancer types have been extensively explored. However, the related exploration based on transcriptome data is lacking. In this study we explored gene expression profiles across 33 human cancer types using The Cancer Genome Atlas (TCGA) data. We identified consistently upregulated genes (such as E2F1, EZH2, FOXM1, MYBL2, PLK1, TTK, AURKA/B and BUB1) and consistently downregulated genes (such as SCARA5, MYOM1, NKAPL, PEG3, USP2, SLC5A7 and HMGCLL1) across various cancers...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28338656/focal-adhesion-kinase-depletion-reduces-human-hepatocellular-carcinoma-growth-by-repressing-enhancer-of-zeste-homolog-2
#2
Daniela Gnani, Ilaria Romito, Simona Artuso, Marco Chierici, Cristiano De Stefanis, Nadia Panera, Annalisa Crudele, Sara Ceccarelli, Elena Carcarino, Valentina D'Oria, Manuela Porru, Ezio Giorda, Karin Ferrari, Luca Miele, Erica Villa, Clara Balsano, Diego Pasini, Cesare Furlanello, Franco Locatelli, Valerio Nobili, Rossella Rota, Carlo Leonetti, Anna Alisi
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in humans. The focal adhesion tyrosine kinase (FAK) is often over-expressed in human HCC and FAK inhibition may reduce HCC cell invasiveness. However, the anti-oncogenic effect of FAK knockdown in HCC cells remains to be clarified. We found that FAK depletion in HCC cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes...
March 24, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28173837/insulin-like-growth-factor-1-receptor-activation-promotes-mammary-gland-tumor-development-by-increasing-glycolysis-and-promoting-biomass-production
#3
Bas Ter Braak, Christine L Siezen, Joo S Lee, Pooja Rao, Charlotte Voorhoeve, Eytan Ruppin, Jan Willem van der Laan, Bob van de Water
BACKGROUND: The insulin-like growth factor 1 (IGF1) signaling axis plays a major role in tumorigenesis. In a previous experiment, we chronically treated mice with several agonists of the IGF1 receptor (IGF1R). We found that chronic treatment with insulin analogues with high affinity towards the IGF1R (IGF1 and X10) decreased the mammary gland tumor latency time in a p53(R270H/+)WAPCre mouse model. Frequent injections with insulin analogues that only mildly activated the IGF1R in vivo (glargine and insulin) did not significantly decrease the tumor latency time in this mouse model...
February 7, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28099249/immunohistochemical-antibody-panel-for-the-differential-diagnosis-of-pancreatic-ductal-carcinoma-from-gastrointestinal-contamination-and-benign-pancreatic-duct-epithelium-in-endoscopic-ultrasound-guided-fine-needle-aspiration
#4
Ayako Furuhata, Sachiko Minamiguchi, Hiroyuki Shirahase, Yuzo Kodama, Souichi Adachi, Takaki Sakurai, Hironori Haga
OBJECTIVES: The diagnosis of pancreatic ductal adenocarcinoma (PDAC) by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can be challenging to distinguish tumor cells from benign epithelium (BE). The aim of the present study was to set a minimal antibody panel to differentiate PDAC from contaminated BE in EUS-FNA specimens. METHODS: Immunohistochemistry using claudin 4, EZH2, Ki-67, maspin, p53, and S100P was performed on tissue microarray sections containing 53 PDACs and 33 BE as well as cell blocks of EUS-FNA including 53 PDACs and 22 BE...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28089541/insulin-like-growth-factor-ii-mrna-binding-protein-3-imp3-is-a-marker-that-predicts-presence-of-invasion-in-papillary-biliary-tumors
#5
Motoko Sasaki, Yasunori Sato
Biliary tumors showing intraductal papillary growth (Pap-BTs) include intraductal papillary neoplasm of the bile duct (IPNB) and papillary cholangiocarcinoma (CC). A differential diagnosis between IPNB and papillary CC currently remains challenging. The aim of the present study is to identify histological features and immunohistochemical markers of malignant potential such as tumor invasion in Pap-BTs. Subjects comprised 37 patients with Pap-BT (intrahepatic and perihilar [proximal], 27: 17 noninvasive and 10 invasive; distal, 10: all invasive)...
April 2017: Human Pathology
https://www.readbyqxmd.com/read/28078190/loss-of-quiescence-and-self-renewal-capacity-of-hematopoietic-stem-cell-in-an-in-vitro-leukemic-niche
#6
Natalia-Del Pilar Vanegas, Jean-Paul Vernot
BACKGROUND: Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. METHODS: A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/27927750/mdm2-as-a-chromatin-modifier
#7
Magdalena Wienken, Ute M Moll, Matthias Dobbelstein
Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimethylation, and PRC1 (via RING1B) mediates histone 2A lysine 119 (H2AK119) monoubiquitination. Both PRCs mostly support a compact and transcriptionally silent chromatin structure...
February 1, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27803714/senescence-associated-molecular-and-epigenetic-alterations-in-mesenchymal-stem-cell-cultures-from-amniotic-fluid-of-normal-and-fetus-affected-pregnancy
#8
Jūratė Savickienė, Sandra Baronaitė, Aistė Zentelytė, Gražina Treigytė, Rūta Navakauskienė
Human amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) are interesting for their multilineage differentiation potential and wide range of therapeutic applications due to the ease of culture expansion. However, MSCs undergo replicative senescence. So far, the molecular mechanisms that underlie fetal diseases and cell senescence are still poorly understood. Here, we analyzed senescence-associated morphologic, molecular, and epigenetic characteristics during propagation of MSCs derived from AF of normal and fetus-affected pregnancy...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27793210/investigation-of-ezh2-pathways-for-novel-epigenetic-treatment-strategies-in-oropharyngeal-cancer
#9
Sherif Idris, Cameron Lindsay, Morris Kostiuk, Colin Andrews, David W J Côté, Daniel A O'Connell, Jeffrey Harris, Hadi Seikaly, Vincent L Biron
BACKGROUND: In recent decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising worldwide as a result of increasing oncogenic human papillomavirus (HPV) infections in the oropharynx. EZH2 is an epigenetic regulatory protein associated with tumor aggressiveness and negative survival outcomes in several human cancers. We aimed to determine the role of EZH2 as a potential therapeutic epigenetic target in HPV-positive and negative OPSCC. METHODS: The expression of EZH2 was measured by immunohistochemistry (IHC) and droplet digital PCR (ddPCR) in 2 HPV-positive and 2 HPV-negative cell lines...
October 28, 2016: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/27719642/bona-fide-targets-of-deregulated-micrornas-in-non-small-cell-lung-cancer-as-tool-to-identify-novel-therapeutic-targets-a-review
#10
Monica Cipollini, Stefano Landi, Federica Gemignani
BACKGROUND: Non-small-cell lung cancer (NSCLC) is an aggressive neoplasm with a poor survival and novel therapies are urgently needed. The study of deregulated micro-RNAs (dereg-miRs) could constitute a strategy helping to detect specific genes playing a relevant role in the disease. Thus, the oncoproteins encoded by these genes could be exploited as novel therapeutic targets to be inhibited by small molecules, aptamers, or monoclonal antibodies. METHODS: The present review is focused on candidate genes having convincing biological evidences to be both bona fide targets for dereg-miRs and playing a role in NSCLC progression...
October 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27634879/large-variety-in-a-panel-of-human-colon-cancer-organoids-in-response-to-ezh2-inhibition
#11
Martijn A J Koppens, Gergana Bounova, Paulien Cornelissen-Steijger, Nienke de Vries, Owen J Sansom, Lodewyk F A Wessels, Maarten van Lohuizen
EZH2 inhibitors have gained great interest for their use as anti-cancer therapeutics. However, most research has focused on EZH2 mutant cancers and recently adverse effects of EZH2 inactivation have come to light. To determine whether colorectal cancer cells respond to EZH2 inhibition and to explore which factors influence the degree of response, we treated a panel of 20 organoid lines derived from human colon tumors with different concentrations of the EZH2 inhibitor GSK126. The resulting responses were associated with mutation status, gene expression and responses to other drugs...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27610467/interfering-ezh2-expression-reverses-the-cisplatin-resistance-in-human-ovarian-cancer-by-inhibiting-autophagy
#12
Yang Sun, Long Jin, Jia-Hua Liu, Yu-Xia Sui, Li-Li Han, Xiao-Li Shen
We aimed to determine the effects of the inhibition of enhancer of zeste homolog 2 (EZH2) gene expression on the cisplatin resistance of the human ovarian cancer cell line, SKOV3/DDP, and to identify the underlying mechanisms. SKOV3/DDP cells were stably transfected with pSUPER-EZH2 (EZH2 RNA interference plasmid) or pcDNA3.1-EZH2 (EZH2 gene overexpression plasmid) using the lipofection method. Real-time fluorescence quantitative reverse transcription polymerase chain reaction and western blotting confirmed that EZH2 expression was downregulated in pSUPER-EZH2-transfected cells...
September 2016: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27517917/the-antitumor-effect-of-metformin-is-mediated-by-mir-26a-in-breast-cancer
#13
Paula Cabello, Begoña Pineda, Eduardo Tormo, Ana Lluch, Pilar Eroles
Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this effect; likewise, this miRNA has also been associated with survival/apoptosis processes in breast cancer. Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer...
August 10, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27472460/ezh2-mediated-puma-gene-repression-regulates-non-small-cell-lung-cancer-cell-proliferation-and-cisplatin-induced-apoptosis
#14
Haidan Liu, Wei Li, Xinfang Yu, Feng Gao, Zhi Duan, Xiaolong Ma, Shiming Tan, Yunchang Yuan, Lijun Liu, Jian Wang, Xinmin Zhou, Yifeng Yang
Polycomb group (PcG) proteins are highly conserved epigenetic effectors that maintain the silenced state of genes. EZH2 is the catalytic core and one of the most important components of the polycomb repressive complex 2 (PRC2). In non-small cell lung cancer (NSCLC) cells and primary lung tumors, we found that PRC2 components, including EZH2, are overexpressed. High levels of EZH2 protein were associated with worse overall survival rate in NSCLC patients. RNA interference mediated attenuation of EZH2 expression blunted the malignant phenotype in this setting, exerting inhibitory effects on cell proliferation, anchorage-independent growth, and tumor development in a xenograft mouse model...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27461342/hypomethylation-coordinates-antagonistically-with-hypermethylation-in-cancer-development-a-case-study-of-leukemia
#15
Garima Kushwaha, Mikhail Dozmorov, Jonathan D Wren, Jing Qiu, Huidong Shi, Dong Xu
BACKGROUND: Methylation changes are frequent in cancers, but understanding how hyper- and hypomethylated region changes coordinate, associate with genomic features, and affect gene expression is needed to better understand their biological significance. The functional significance of hypermethylation is well studied, but that of hypomethylation remains limited. Here, with paired expression and methylation samples gathered from a patient/control cohort, we attempt to better characterize the gene expression and methylation changes that take place in cancer from B cell chronic lymphocyte leukemia (B-CLL) samples...
2016: Human Genomics
https://www.readbyqxmd.com/read/27432063/over-expression-of-mir-200c-suppresses-invasion-and-restores-methotrexate-sensitivity-in-lung-cancer-a549-cells
#16
Wulin Shan, Xiaolei Zhang, Ming Li, Fang Deng, Jing Zhang
MicroRNAs have become recognized as key players in the development of malignancy. MiR-200c can function as a tumor suppressor gene. However, the effect of miR-200c on methotrexate resistance remains unclear to date. This study aims to evaluate the function of miR-200c in lung cancer A549 cells. The data presented in our study demonstrated that the expression of miR-200c was down-regulated in methotrexate-resistant A549 cells. Over expression of miR-200c could significantly inhibit cell proliferation, induce G0/G1 cell cycle arrest and induce cell apoptosis...
November 30, 2016: Gene
https://www.readbyqxmd.com/read/27323178/expression-and-clinical-implications-of-enhancer-of-zeste-homolog-2-and-p53-protein-in-squamous-cell-carcinoma-and-precancerous-lesions-in-the-cervix
#17
H M Zhang, S Q Chen, S Z Yao
We investigated the expression and clinical implications of enhancer of Zeste homolog 2 (EZH2) and p53 protein in cervical squamous cell carcinoma (SCC) and precancerous lesions. EZH2 and p53 expressions in SCC (168), cervical intraepithelial neoplasia (CIN)-I (19), CIN-II (35), and normal tissues (30) were detected by streptavidin-peroxidase-conjugation. The correlation between co-expression of EZH2 and p53 protein and the clinic pathological features and prognosis of SCC were discussed. The positive expression rates of EZH2 and p53 were 6...
June 16, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27247549/identification-of-differentially-expressed-genes-associated-with-the-enhancement-of-x-ray-susceptibility-by-rita-in-a-hypopharyngeal-squamous-cell-carcinoma-cell-line-fadu
#18
Jinwei Luan, Xianglan Li, Rutao Guo, Shanshan Liu, Hongyu Luo, Qingshan You
BACKGROUND: Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. MATERIALS AND METHODS: The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses...
June 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27149985/ezh2-is-overexpressed-in-adrenocortical-carcinoma-and-is-associated-with-disease-progression
#19
Coralie Drelon, Annabel Berthon, Mickael Mathieu, Bruno Ragazzon, Rork Kuick, Houda Tabbal, Amandine Septier, Stéphanie Rodriguez, Marie Batisse-Lignier, Isabelle Sahut-Barnola, Typhanie Dumontet, Jean-Christophe Pointud, Anne-Marie Lefrançois-Martinez, Silvère Baron, Thomas J Giordano, Jérôme Bertherat, Antoine Martinez, Pierre Val
Adrenal Cortex Carcinoma (ACC) is an aggressive tumour with poor prognosis. Common alterations in patients include constitutive WNT/β-catenin signalling and overexpression of the growth factor IGF2. However, the combination of both alterations in transgenic mice is not sufficient to trigger malignant tumour progression, suggesting that other alterations are required to allow development of carcinomas. Here, we have conducted a study of publicly available gene expression data from three cohorts of ACC patients to identify relevant alterations...
July 1, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27135738/an-oncogenic-ezh2-mutation-induces-tumors-through-global-redistribution-of-histone-3-lysine-27-trimethylation
#20
George P Souroullas, William R Jeck, Joel S Parker, Jeremy M Simon, Jie-Yu Liu, Joshiawa Paulk, Jessie Xiong, Kelly S Clark, Yuri Fedoriw, Jun Qi, Christin E Burd, James E Bradner, Norman E Sharpless
B cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase (EZH2), but the carcinogenic role of these mutations is unclear. Here we describe a mouse model in which the most common somatic Ezh2 gain-of-function mutation (EZH2(Y646F) in human; Ezh2(Y641F) in mouse) is conditionally expressed. Expression of Ezh2(Y641F) in mouse B cells or melanocytes caused high-penetrance lymphoma or melanoma, respectively. Overexpression of the anti-apoptotic protein Bcl2, but not the oncoprotein Myc, or loss of the tumor suppressor protein p53 (encoded by Trp53 in mice) further accelerated lymphoma progression...
June 2016: Nature Medicine
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