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Katsuhiko Masudo, Nobuyasu Suganuma, Hirotaka Nakayama, Takashi Oshima, Yasushi Rino, Hiroyuki Iwasaki, Kenichi Matsuzu, Kiminori Sugino, Koichi Ito, Tetsuo Kondo, Yoshiyasu Nakamura, Mitsuyo Yoshihara, Munetaka Masuda, Yohei Miyagi
BACKGROUND/AIM: Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes, which are key factors in the regulation of cell proliferation and differentiation. EZH2 is overexpressed in many malignancies. We analyzed EZH2 protein expression levels in different histological subtypes of thyroid cancer to examine its utility as a prognostic factor. MATERIALS AND METHODS: We examined EZH2 protein expression by immunohistochemistry in tissue samples from 67 cases of poorly differentiated (PDTC) and 48 cases of anaplastic thyroid carcinoma (ATC), and in samples of adjacent normal and differentiated thyroid carcinoma (DTC)...
January 2018: In Vivo
S Fujita, D Honma, N Adachi, K Araki, E Takamatsu, T Katsumoto, K Yamagata, K Akashi, K Aoyama, A Iwama, I Kitabayashi
Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer originating from rare populations of leukemia stem cells (LSCs). AML relapse after conventional chemotherapy is caused by a remaining population of drug-resistant LSCs. Selective targeting of the chemoresistant population is a promising strategy for preventing and treating AML relapse. Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27 to maintain the stemness of LSCs. Here, we show that quiescent LSCs expressed the highest levels of enhancer of zeste (EZH) 1 and EZH2, the PRC2 catalytic subunits, in the AML hierarchy, and that dual inactivation of EZH1/2 eradicated quiescent LSCs to cure AML...
April 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuanyun Li, William T Pu, Aibin He
RATIONALE: Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. OBJECTIVE: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration...
July 7, 2017: Circulation Research
Weihua Zhang, Jun Lin, Peng Wang, Jian Sun
Non-small cell lung cancer (NSCLC) is the major cause of lung cancer-related deaths. Erlotinib is an effective drug for NSCLC patients, but its effect in advanced NSCLC is compromised because of the drug resistance. The mechanism of erlotinib resistance in NSCLC is largely unknown. In the current study, we found that erlotinib treatment down-regulated miR-17-5p level in A549 cells and miR-17-5p was lower in acquired erlotinib-resistant A549 cells (A549-ER) compared with erlotinib-sensitive A549 cells. Consistently, miR-17-5p was down-regulated in the tumor tissues and the plasma of erlotinib-resistant NSCLC patients in comparison to those who are sensitive to erlotinib...
September 16, 2016: Journal of Drug Targeting
Takafumi Minami, Tomoko Minami, Nobutaka Shimizu, Yutaka Yamamoto, Marco A De Velasco, Masahiro Nozawa, Kazuhiro Yoshimura, Nanae Harashima, Mamoru Harada, Hirotsugu Uemura
Analyses on reactivity of anti-cancer cytotoxic T lymphocytes (CTLs) and clinical application of peptide-based anti-cancer vaccine have been mainly focused on patients with HLA-A2 or -A24 alleles. In this study, we identified an enhancer of zeste homolog (EZH) 2-derived peptide applicable for anti-cancer vaccine for prostate cancer patients with HLA-A3 supertype alleles. Five EZH2-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were functionally screened for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A3 supertype allele(+) prostate cancer patients...
May 2015: International Immunopharmacology
Anees Thajudeen, Warren M Jackman, Brian Stewart, Ivan Cokic, Hiroshi Nakagawa, Michael Shehata, Allen M Amorn, Avinash Kali, Ezh Liu, Doron Harlev, Nathan Bennett, Rohan Dharmakumar, Sumeet S Chugh, Xunzhang Wang
BACKGROUND: Endocardial mapping for scars and abnormal electrograms forms the most essential component of ventricular tachycardia ablation. The utility of ultra-high resolution mapping of ventricular scar was assessed using a multielectrode contact mapping system in a chronic canine infarct model. METHODS: Chronic infarcts were created in five anesthetized dogs by ligating the left anterior descending coronary artery. Late gadolinium-enhanced magnetic resonance imaging (LGE MRI) was obtained 4...
June 2015: Pacing and Clinical Electrophysiology: PACE
Phillip A Dumesic, Christina M Homer, James J Moresco, Lindsey R Pack, Erin K Shanle, Scott M Coyle, Brian D Strahl, Danica G Fujimori, John R Yates, Hiten D Madhani
We characterize the Polycomb system that assembles repressive subtelomeric domains of H3K27 methylation (H3K27me) in the yeast Cryptococcus neoformans. Purification of this PRC2-like protein complex reveals orthologs of animal PRC2 components as well as a chromodomain-containing subunit, Ccc1, which recognizes H3K27me. Whereas removal of either the EZH or EED ortholog eliminates H3K27me, disruption of mark recognition by Ccc1 causes H3K27me to redistribute. Strikingly, the resulting pattern of H3K27me coincides with domains of heterochromatin marked by H3K9me...
January 15, 2015: Cell
Woo Kyun Bae, Keunsoo Kang, Ji Hoon Yu, Kyung Hyun Yoo, Valentina M Factor, Kosuke Kaji, Matthias Matter, Snorri Thorgeirsson, Lothar Hennighausen
To investigate the role of enhancer of zeste homolog (EZH) 1 and EZH2 in liver homeostasis, mice were generated that carried Ezh1(-/-) and EZH2(fl/fl) alleles and an Alb-Cre transgene. Only the combined loss of EZH1 and EZH2 in mouse hepatocytes caused a depletion of global trimethylation on Lys 27 of histone H3 (H3K27me3) marks and the specific loss of over ∼1900 genes at 3 mo of age. Ezh1(-/-),Ezh2(fl/fl)Alb-Cre mice exhibited progressive liver abnormalities manifested by the development of regenerative nodules and concomitant periportal fibrosis, inflammatory infiltration, and activation of A6-positive hepatic progenitor cells at 8 mo of age...
May 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Huimin Zhang, Shuqin Chen, Gang Niu, Hongye Jiang, Shuzhong Yao
OBJECTIVE: To investigate the expression and clinical significance of enhancer of zeste homolog 2 (EZH2) and p53 proteins in cervical squamous cell carcinoma (SCC) and cervical intraepithelial neoplasia (CIN). METHODS: The expression and distribution of EZH2 and p53 were determined with reference to clinicopathological features and patient survival. 168 cervical SCC, 19 CINII, 35 CINIII patients and 30 normal control cases were collected for immunohistochemical analysis...
August 2014: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Polyxeni Nicolopoulou-Stamati, Angelos Tsipis, George Chelidonis, Efstratios Patsouris, Pauline Athanassiadou, Maria Gonidi, Anna Maria Athanassiadou
BACKGROUND: Cytological differential diagnosis of atypical hyperplasia and well differentiated breast carcinoma may be challenging, because sometimes there is an overlap between the cytomorphological features of these lesions. The aim of the study was to investigate COX-2, EZH-2, p53 expression in carcinomas and the gray zone of breast cytology categories of atypical hyperplastic lesions with regard to biological behavior of the tumor. METHODS: FNA speciments from 100 patients with breast hyperplastic lesions and cancer were investigated by immunocytochemistry and a quantitative analysis for COX-2, p53, and EZH-2...
April 2015: Diagnostic Cytopathology
Shuangping Guo, John K C Chan, Javeed Iqbal, Timothy McKeithan, Kai Fu, Bin Meng, Yi Pan, Wah Cheuk, Donglan Luo, Ruian Wang, Weiwei Zhang, Timothy C Greiner, Wing C Chan
PURPOSE: Gain-of-function mutations of enhancer of Zeste homolog 2 (EZH2) occur frequently in diffuse large B-cell lymphomas and in follicular lymphomas. However, the frequency of EZH2 mutation in Chinese follicular lymphomas and the potential targets affected by this mutation are unknown. EXPERIMENTAL DESIGN: We determined EZH2 codon 641 mutations in Chinese follicular lymphomas (n = 124) and compared them with Western follicular lymphomas (n = 70) using a sensitive pyrosequencing assay...
June 15, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jinsook Son, Steven S Shen, Raphael Margueron, Danny Reinberg
Polycomb-repressive complex 2 (PRC2) comprises specific members of the Polycomb group of epigenetic modulators. PRC2 catalyzes methylation of histone H3 at Lys 27 (H3K27me3) through its Enhancer of zeste (Ezh) constituent, of which there are two mammalian homologs: Ezh1 and Ezh2. Several ancillary factors, including Jarid2, modulate PRC2 function, with Jarid2 facilitating its recruitment to target genes. Jarid2, like Ezh2, is present in poorly differentiated and actively dividing cells, while Ezh1 associates with PRC2 in all cells, including resting cells...
December 15, 2013: Genes & Development
Hyun Jung Lee, Dong Hoon Shin, Kyung Bin Kim, Nari Shin, Won Young Park, Jung Hee Lee, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Mee Young Sol
Polycomb group (PcG) proteins are evolutionarily conserved regulators of gene expression that contribute to normal lymphocyte development, and are involved in malignant transformation of these cells. Recently, BMI1 and EZH2 have been shown to be involved in lymphomagenesis and oncogenesis. We tried to elucidate the role of EZH2 as a prognostic factor for diffuse large B-cell lymphoma (DLBCL). High-level expression of EZH2 (EZH2 ≥ 70%) was associated with superior overall survival (OS) of 85.8% compared to low expression (EZH2 < 70%), with OS of 44...
September 2014: Leukemia & Lymphoma
Brooke M Swalm, Kenneth K Hallenbeck, Christina R Majer, Lei Jin, Margaret Porter Scott, Mikel P Moyer, Robert A Copeland, Tim J Wigle
H3K27 (histone H3 Lys27) methylation is an important epigenetic modification that regulates gene transcription. In humans, EZH (enhancer of zeste homologue) 1 and EZH2 are the only enzymes capable of catalysing methylation of H3K27. There is great interest in understanding structure-function relationships for EZH2, as genetic alterations in this enzyme are thought to play a causal role in a number of human cancers. EZH2 is challenging to study because it is only active in the context of the multi-subunit PRC2 (polycomb repressive complex 2)...
July 15, 2013: Biochemical Journal
Anna-Maria Athanassiadou, Andreas C Lazaris, Efstratios Patsouris, Angelos Tsipis, George Chelidonis, Kyriaki Aroni
The development and progression of squamous cell carcinoma (SCC) of the skin is characterized by an accumulation of molecular changes. The aim of this study was to investigate the association of the immunohistochemical expression of cyclooxygenase-2 (COX-2), enhancer of zeste homolog 2 (EZH-2), and p53 in actinic keratosis (AK) and SCC and detect any differences between invasive and preinvasive squamous epidermal lesions. Forty-three cases with AK, 38 with SCC, and 9 with SCC arising on AK (SCC/AK) were studied...
June 2013: American Journal of Dermatopathology
Valeria Visconte, Heesun J Rogers, Jarnail Singh, John Barnard, Manoj Bupathi, Fabiola Traina, James McMahon, Hideki Makishima, Hadrian Szpurka, Anna Jankowska, Andres Jerez, Mikkael A Sekeres, Yogen Saunthararajah, Anjali S Advani, Edward Copelan, Haruhiko Koseki, Kyoichi Isono, Richard A Padgett, Sami Osman, Kazunori Koide, Christine O'Keefe, Jaroslaw P Maciejewski, Ramon V Tiu
Whole exome/genome sequencing has been fundamental in the identification of somatic mutations in the spliceosome machinery in myelodysplastic syndromes (MDSs) and other hematologic disorders. SF3B1, splicing factor 3b subunit 1 is mutated in 60%-80% of refractory anemia with ring sideroblasts (RARS) and RARS associated with thrombocytosis (RARS-T), 2 distinct subtypes of MDS and MDS/myeloproliferative neoplasms (MDSs/MPNs). An idiosyncratic feature of RARS/RARS-T is the presence of abnormal sideroblasts characterized by iron overload in the mitochondria, called RS...
October 18, 2012: Blood
Kyung Hyun Yoo, Lothar Hennighausen
Histone modifications are thought to control the regulation of genetic programs in normal physiology and cancer. Methylation (mono-, di-, and tri-methylation) on histone H3 lysine (K) 27 induces transcriptional repression, and thereby participates in controlling gene expression patterns. Enhancer of zeste (EZH) 2, a methyltransferase and component of the polycomb repressive complex 2 (PRC2), plays an essential role in the epigenetic maintenance of the H3K27me3 repressive chromatin mark. Abnormal EZH2 expression has been associated with various cancers including breast cancer...
2012: International Journal of Biological Sciences
Lu Lu, Lei Li, Xiang Lü, Xue-song Wu, De-pei Liu, Chih-chuan Liang
OBJECTIVE: To study the regulatory rolesof SIRT1 on EZH2 expression and the further effects on EZH 2’ s repression of target gene expression. METHODS: The stable SIRT1 RNAi and Control RNAi HeLa cells were established by infection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2...
June 2011: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
Katherine E Hankowski, Naohiro Terada
No abstract text is available yet for this article.
July 15, 2011: Cell Cycle
Giuseppina Caretti, Daniela Palacios, Vittorio Sartorelli, Pier Lorenzo Puri
Polycomb group (PcG) proteins regulate gene expression in embryonic and adult stem cells, but the mechanisms responsible for PcG gene targeting and regulation remain largely unknown. Recent evidence shows that EZH2, the enzymatic subunit of Polycomb Repressive Complex 2 (PRC2), is a nuclear phosphoprotein linking cell-cycle-intrinsic or extracellular signals to specific epigenetic signatures.
March 4, 2011: Cell Stem Cell
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