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p53 Ezh2

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https://www.readbyqxmd.com/read/29760602/sodium-valproate-inhibits-small-cell-lung-cancer-tumor-growth-on-the-chicken-embryo-chorioallantoic-membrane-and-reduces-the-p53-and-ezh2-expression
#1
Lina Šlekienė, Donatas Stakišaitis, Ingrida Balnytė, Angelija Valančiūtė
The study aims to test the effect of different sodium valproate (NaVP) doses on small cell lung cancer NCI-H146 cells tumor in chicken embryo chorioallantoic membrane (CAM) model. Xenografts were investigated in the following groups: nontreated control and 5 groups treated with different NaVP doses (2, 3, 4, 6, and 8 mmol/L). Invasion of tumors into CAM in the nontreated group reached 76%. Tumors treated with 8 mmol/L NaVP doses significantly differed in tumor invasion frequency from the control and those treated with 2 mmol/L ( P < ...
April 2018: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/29676649/asbestos-induces-epigenetic-repression-of-ras-association-domain-containing-protein-1-p16-kinase-4a-inhibitor-and-p14-alternative-reading-frame-in-normal-human-mesothelial-cells
#2
Sichuan Xi, Eden C Payabyab, David M Straughan, Emily S Reardon, Mary Zhang, Julie A Hong, R Taylor Ripley, Chuong D Hoang, David S Schrump
RATIONALE: Whereas asbestos burden has been linked to cytogenetic alterations in malignant pleural mesotheliomas, epigenetic aberrations induced by these fibers have not been fully delineated. OBJECTIVES: The objective of this study was to establish an in vitro model to characterize early epigenetic events potentially contributing to malignant pleural mesothelioma. METHODS: Normal human mesothelial cells (LP9 and LP3) were cultured with or without crocidolite asbestos fibers (1 or 2 μg/cm2 ) for up to 10 days...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29615405/the-enigma-of-monosomy-7
#3
Toshiya Inaba, Hiroaki Honda, Hirotaka Matsui
Since a report of some 50 years ago describing refractory anemia associated with group C monosomy, monosomy 7 (-7) and interstitial deletions of chromosome 7 [del(7q)] have been established as one of the most frequent chromosomal aberrations found in essentially all types of myeloid tumors regardless of patient age and disease etiology. In the last century, researchers sought recessive myeloid tumor-suppressor genes by attempting to determine commonly-deleted regions (CDRs) in del(7q) patients. However, these efforts were not successful...
April 3, 2018: Blood
https://www.readbyqxmd.com/read/29540569/an-ezh2-mediated-epigenetic-mechanism-behind-p53-dependent-tissue-sensitivity-to-dna-damage
#4
Gamze Kuser-Abali, Lu Gong, Jiawei Yan, Qingqing Liu, Weiqi Zeng, Amanda Williamson, Chuan Bian Lim, Mary Ellen Molloy, John B Little, Lei Huang, Zhi-Min Yuan
Renewable tissues exhibit heightened sensitivity to DNA damage, which is thought to result from a high level of p53. However, cell proliferation in renewable tissues requires p53 down-regulation, creating an apparent discrepancy between the p53 level and elevated sensitivity to DNA damage. Using a combination of genetic mouse models and pharmacologic inhibitors, we demonstrate that it is p53-regulated MDM2 that functions together with MDMX to regulate DNA damage sensitivity by targeting EZH2 (enhancer of zeste homolog 2) for ubiquitination/degradation...
March 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29489508/ezh2-expression-in-intestinal-neuroendocrine-tumors
#5
Pinuccia Faviana, Riccardo Marconcini, Sergio Ricci, Luca Galli, Piero Lippolis, Fabiola Farci, Maura Castagna, Laura Boldrini
Neuroendocrine tumors (NETs) arise from the cells present throughout the diffuse endocrine system. These neoplasms were previously regarded as rare, but in fact are increasing in incidence (3.65/100 000 individuals/y). Enhancer of zeste homolog 2 (EZH2) plays a crucial role in cell cycle regulation, and it was reported to be overexpressed in several tumors. The aim of the study was to investigate EZH2 expression, also related with proliferation rate, and p53 expression in NETs of the intestine encompassing a group of tumors primary to the stomach, appendix, small intestine, and colon...
February 27, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29403289/association-of-clinicopathologic-characteristics-and-outcomes-with-ezh2-expression-in-patients-with-breast-cancer-in-east-azerbaijan-iran
#6
Farnaz Boostani, Roya Dolatkhah, Ashraf Fakhrjou, Faris Farassati, Zohreh Sanaat
Background: Recently, it was found that the overexpression and mutation status of EZH2 affect cancer progression and patient outcome in several human tumors. We aimed to evaluate the clinicopathologic significance of EZH2 in patients with breast cancer. Methods: This was an analytical descriptive study of surgical specimens of primary breast tumors. Specimens were analyzed immunohistochemically for EZH2 , estrogen receptor, progesterone receptor, Ki-67, P53, and human epidermal growth factor receptor 2 (HER2) expressions...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29389953/role-of-metastasis-associated-lung-adenocarcinoma-transcript-1-malat-1-in-pancreatic-cancer
#7
Yating Cheng, Parisa Imanirad, Indira Jutooru, Erik Hedrick, Un-Ho Jin, Aline Rodrigues Hoffman, Jeann Leal de Araujo, Benjamin Morpurgo, Andrei Golovko, Stephen Safe
Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a long non-coding RNA (lncRNA) that is a negative prognostic factor for patients with pancreatic cancer and several other tumors. In this study, we show that knockdown of MALAT-1 in Panc1 and other pancreatic cancer cell lines decreases cell proliferation, survival and migration. We previously observed similar results for the lncRNAs HOTTIP and HOTAIR in Panc1 cells; however, RNAseq comparison of genes regulated by MALAT-1 shows minimal overlap with HOTTIP/HOTAIR-regulated genes...
2018: PloS One
https://www.readbyqxmd.com/read/29371630/necessity-of-p53-binding-to-the-cdh1-locus-for-its-expression-defines-two-epithelial-cell-types-differing-in-their-integrity
#8
Tsukasa Oikawa, Yutaro Otsuka, Yasuhito Onodera, Mei Horikawa, Haruka Handa, Shigeru Hashimoto, Yutaka Suzuki, Hisataka Sabe
TP53 mutation (i.e., loss of normal-p53) may evoke epithelial-mesenchymal transition (EMT), which was previously attributed to loss of certain miRNAs. However, not all epithelial cells undergo EMT upon TP53 mutation, and the p53-miRNA axis may not fully explain p53 function in epithelial integrity. We here show two modes of epithelial integrity: one involves p53-binding to a nucleotide region and the other does not. In the former, p53 binds to the CDH1 (encoding E-cadherin) locus to antagonize EZH2-mediated H3K27 trimethylation (H3K27me3) to maintain high levels of acetylation of H3K27 (H3K27ac)...
January 25, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29113297/long-non-coding-rna-profile-in-mantle-cell-lymphoma-identifies-a-functional-lncrna-ror1-as1-associated-with-ezh2-prc2-complex
#9
Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098582/oxidative-stress-and-cell-cycle-arrest-induced-by-short-term-exposure-to-dustfall-pm2-5-in-a549-cells
#10
Jie Yang, Tingting Huo, Xu Zhang, Jie Ma, Yulin Wang, Faqin Dong, Jianjun Deng
It was reported that in vitro short-term exposure to PM2.5 caused different lung diseases through inflammatory response, immune toxicity, oxidative stress, and genetic mutations. However, the complex molecular biological mechanism for its toxicity had not been fully elucidated. Therefore, the present study investigated the cytotoxicity, oxidative damage, mitochondria damage, apoptosis, and cell cycle arrest of NX and QH PM2.5 in A549 cells. Further, cell cycle arrest-related gene levels in PM2.5-induced A549 cells were also detected...
November 2, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29032608/microrna-profiling-reveals-dysregulated-micrornas-and-their-target-gene-regulatory-networks-in-cemento-ossifying-fibroma
#11
Thaís Dos Santos Fontes Pereira, João Artur Ricieri Brito, André Luiz Sena Guimarães, Carolina Cavaliéri Gomes, Júlio Cesar Tanos de Lacerda, Wagner Henriques de Castro, Roney Santos Coimbra, Marina Gonçalves Diniz, Ricardo Santiago Gomez
BACKGROUND: Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of uncertain pathogenesis, and its treatment results in morbidity. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and may represent therapeutic targets. The purpose of the study was to generate a comprehensive miRNA profile of COF compared to normal bone. Additionally, the most relevant pathways and target genes of differentially expressed miRNA were investigated by in silico analysis...
January 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28979810/enhancing-chemotherapy-sensitivity-by-targeting-pcg-via-the-atm-p53-pathway
#12
Shu-Bin Gao, Kang-Li Li, Huan Qiu, Ling-Yu Zhu, Chang-Bao Pan, Yue Zhao, Shu-Hua Wei, Shu Shi, Guang-Hui Jin, Li-Xiang Xue
Histone modification and chromatin remodeling are important events in response to DNA damage, and Polycomb group (PcG) proteins, catalyzing H3K27 methylation, are involved. However, the biological function and mechanism of PcG in DNA damage are not fully understood. Additionally, downstream effectors in hepatocellular carcinoma (HCC) remain unclear. The present study investigated the biological and mechanistic roles of PcG in the DNA damage response induced by chemotherapeutic drugs in HCC. It was found that chemotherapy drugs, such as epirubicin (EPB) and mitomycin C (MMC), effectively blocked expression of PcG in p53-wild-type HepG2 cells but not in PLC/PRF5 and Hep3B cells with p53 mutation or deletion...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28931330/sequential-molecular-changes-and-dynamic-oxidative-stress-in-high-grade-serous-ovarian-carcinogenesis
#13
Hiroshi Kobayashi, Kenji Ogawa, Naoki Kawahara, Kana Iwai, Emiko Niiro, Sachiko Morioka, Yuki Yamada
The mechanism of high-grade serous ovarian cancer (HGSC) development remains elusive. This review outlines recent advances in the understanding of sequential molecular changes associated with the development of HGSC, as well as describes oxidative stress-induced genomic instability and carcinogenesis. This article reviews the English language literature between 2005 and 2017. Clinicopathological features analysis provides a sequential progression of fallopian tubal epithelium to precursor lesions to type 2 HGSC...
October 2017: Free Radical Research
https://www.readbyqxmd.com/read/28811894/the-conceptual-advances-of-carcinogenic-sequence-model-in-high-grade-serous-ovarian-cancer
#14
Hiroshi Kobayashi, Kana Iwai, Emiko Niiro, Sachiko Morioka, Yuki Yamada, Kenji Ogawa, Naoki Kawahara
The present review focuses on the current status of molecular pathology in high-grade serous cancer (HGSC) and preneoplastic conditions. This article reviews the English-language literature on HGSC, precursor, fallopian tubal epithelium, secretory cells, ciliated cells, secretory cell expansion, secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC), DNA damage and immunohistochemistry in an effort to identify the precursor-carcinoma sequence in HGSC. The majority of HGSC originates from the fimbriated end of the fallopian tube secretory epithelial cells, while the small part of this disease may develop from ovarian cortical inclusion cyst (CIC)...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28775165/ezh2-palmitoylation-mediated-by-zdhhc5-in-p53-mutant-glioma-drives-malignant-development-and-progression
#15
Xueran Chen, Huihui Ma, Zhen Wang, Shangrong Zhang, Haoran Yang, Zhiyou Fang
Gliomas with mutant p53 occurring in 30% of glioma patients exhibit therapeutic resistance and poor outcomes. In this study, we identify a novel mechanism through which mutant p53 drives cancer cell survival and malignant growth. We documented overexpression of the zinc finger protein ZDHHC5 in glioma compared with normal brain tissue and that this event tightly correlated with p53 mutations. Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28659443/genetic-and-epigenetic-inactivation-of-sestrin1-controls-mtorc1-and-response-to-ezh2-inhibition-in-follicular-lymphoma
#16
Elisa Oricchio, Natalya Katanayeva, Maria Christine Donaldson, Stephanie Sungalee, Joyce P Pasion, Wendy Béguelin, Elena Battistello, Viraj R Sanghvi, Man Jiang, Yanwen Jiang, Matt Teater, Anita Parmigiani, Andrei V Budanov, Fong Chun Chan, Sohrab P Shah, Robert Kridel, Ari M Melnick, Giovanni Ciriello, Hans-Guido Wendel
Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation ( EZH2 Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress...
June 28, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28642877/the-effect-of-sodium-valproate-on-the-glioblastoma-u87-cell-line-tumor-development-on-the-chicken-embryo-chorioallantoic-membrane-and-on-ezh2-and-p53-expression
#17
Dovilė Kavaliauskaitė, Donatas Stakišaitis, Justė Martinkutė, Lina Šlekienė, Arūnas Kazlauskas, Ingrida Balnytė, Vaiva Lesauskaitė, Angelija Valančiūtė
Literature data support evidences that glioblastoma (GBM) patients experience prolonged survival due to sodium valproate (NaVP) treatment. The study assessed the human GBM cell U87 xenograft studied in the chicken embryo chorioallantoic membrane (CAM) model evaluating NaVP effect on tumor. Three groups of tumors (each n = 10) were studied: nontreated, treated with 4 mM, and treated with 8 mM of NaVP. The majority of tumors without NaVP treatment during tumor growth destroyed the chorionic epithelium, invaded the mesenchyme, and induced angiogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28557790/long-non-coding-rna-profile-in-mantle-cell-lymphoma-identifies-a-functional-lncrna-ror1-as1-associated-with-ezh2-prc2-complex
#18
Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522693/histone-h3-3k27m-represses-p16-to-accelerate-gliomagenesis-in-a-murine-model-of-dipg
#19
Francisco J Cordero, Zhiqing Huang, Carole Grenier, Xingyao He, Guo Hu, Roger E McLendon, Susan K Murphy, Rintaro Hashizume, Oren J Becher
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date, the tumor-driving effects of H3...
September 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28490575/ezh2-regulates-the-developmental-timing-of-effectors-of-the-pre-antigen-receptor-checkpoints
#20
Jennifer A Jacobsen, Jennifer Woodard, Malay Mandal, Marcus R Clark, Elizabeth T Bartom, Mikael Sigvardsson, Barbara L Kee
The histone methyltransferase EZH2 is required for B and T cell development; however, the molecular mechanisms underlying this requirement remain elusive. In a murine model of lymphoid-specific EZH2 deficiency we found that EZH2 was required for proper development of adaptive, but not innate, lymphoid cells. In adaptive lymphoid cells EZH2 prevented the premature expression of Cdkn2a and the consequent stabilization of p53, an effector of the pre-Ag receptor checkpoints. Deletion of Cdkn2a in EZH2-deficient lymphocytes prevented p53 stabilization, extended lymphocyte survival, and restored differentiation resulting in the generation of mature B and T lymphocytes...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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