Read by QxMD icon Read


Karolina Nemes, Michael C Frühwald
Malignant Rhabdoid Tumor (MRT) is a rare and highly aggressive malignancy primarily affecting infants and young children. The most common anatomic locations are the central nervous system (AT/RT), the kidneys (RTK) and other soft tissues (eMRT). The genetic origin of this disease is linked to mutations in SMARCB1, a gene encoding a core subunit of the SWI/SNF chromatin-remodeling complex. Areas covered: Conventional multimodal treatment may offer a significant survival benefit to certain patients. It remains to be determined, however, which patients will prove resistant to chemotherapy and need novel therapeutic approaches...
March 12, 2018: Expert Opinion on Therapeutic Targets
Ioannis Anestopoulos, Aristeidis P Sfakianos, Rodrigo Franco, Katerina Chlichlia, Mihalis I Panayiotidis, David J Kroll, Aglaia Pappa
Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin's pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR)...
December 31, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
C Gong, K Fujino, L J Monteiro, A R Gomes, R Drost, H Davidson-Smith, S Takeda, U S Khoo, J Jonkers, D Sproul, E W-F Lam
FOXA1 expression correlates with the breast cancer luminal subtype and patient survival. RNA and protein analysis of a panel of breast cancer cell lines revealed that BRCA1 deficiency is associated with the downregulation of FOXA1 expression. Knockdown of BRCA1 resulted in the downregulation of FOXA1 expression and enhancement of FOXA1 promoter methylation in MCF-7 breast cancer cells, whereas the reconstitution of BRCA1 in Brca1-deficent mouse mammary epithelial cells (MMECs) promoted Foxa1 expression and methylation...
September 24, 2015: Oncogene
Therese M Murphy, Aoife O'Donovan, Niamh Mullins, Cliona O'Farrelly, Amanda McCann, Kevin Malone
OBJECTIVES: Anxiety is associated with elevated levels of the inflammatory cytokine interleukin-6 (IL-6) and an increased risk for diseases with an inflammatory aetiology. In cancer, higher levels of IL-6 have been associated with increased expression of the epigenetic enzymes DNMT1 and Enhancer of Zeste Homolog 2 (EZH2). However, the relationship between IL-6 and DNA methyltransferases (DNMTs) and EZH2 expression has not previously been examined in anxious individuals. METHODS: Global DNA methylation levels were measured using the Methylflash Methylated DNA Quantification Kit and gene expression levels of the DNMT and EZH2 genes in anxious (n=25) and nonanxious individuals (n=22) were compared using quantitative real-time PCR...
April 2015: Psychiatric Genetics
Carmen S Tellez, Marcie J Grimes, Maria A Picchi, Yushi Liu, Thomas H March, Matthew D Reed, Aram Oganesian, Pietro Taverna, Steven A Belinsky
The DNA methyltransferase (DNMT) inhibitor vidaza (5-Azacytidine) in combination with the histone deacetylase inhibitor entinostat has shown promise in treating lung cancer and this has been replicated in our orthotopic lung cancer model. However, the effectiveness of DNMT inhibitors against solid tumors is likely impacted by their limited stability and rapid inactivation by cytidine deaminase (CDA) in the liver. These studies were initiated to test the efficacy of SGI-110, a dinucleotide containing decitabine that is resistant to deamination by CDA, as a single agent and in combination with entinostat...
November 1, 2014: International Journal of Cancer. Journal International du Cancer
Wei Li, Jian Zheng, Jieqiong Deng, Yonghe You, Hongchun Wu, Na Li, Jiachun Lu, Yifeng Zhou
BACKGROUND & AIMS: Thousands of long intergenic non-protein coding RNAs (lincRNAs) have been identified in mammals via genome-wide sequencing studies. Many are functional, but are expressed aberrantly by cancer cells. We investigated whether levels of lincRNAs are altered during the development of esophageal squamous cell carcinoma (ESCC). METHODS: We used quantitative real-time polymerase chain reaction to measure levels of 26 highly conserved lincRNAs in ESCC and surrounding nontumor tissues...
June 2014: Gastroenterology
Naama Dror, Mathilda Mandel, Gad Lavie
Failure of conventional therapies to alleviate glioblastoma (GBM) fosters search for novel therapeutic strategies. These include epigenetic modulators as histone deacetylase inhibitors (HDACi), which relax abnormally compact tumor cell chromatin organization, enabling cells to overcome blockage in differentiation. However, in clinical settings, HDACi efficacy is confined to subsets of hematologic malignancies. We reasoned that molecules targeting multiple epigenetic mechanisms may exhibit superior anti-cancer activities...
2013: PloS One
Mathilde Cheray, Romain Pacaud, Arulraj Nadaradjane, François M Vallette, Pierre-François Cartron
BACKGROUND: Reactivation of silenced tumor suppressor genes by DNMT inhibitors has provided an alternative approach to cancer therapy. However, DNMT inhibitors have also been shown to induce or enhance tumorigenesis via DNA hypomethylation-induced oncogene activation and chromosomal instability. To develop more specific DNMT inhibitors for efficient cancer therapy, we compared the effects of peptides designed to specifically disrupt the interaction of DNMT1 with different proteins. FINDINGS: Our data indicated that the use of an unspecific DNMT inhibitor (5aza-2deoxycytidine), a DNMT1 inhibitor (procainamide) or peptides disrupting the DNMT1/PCNA, DNMT1/EZH2, DNMT1/HDAC1, DNMT1/DNMT3b and DNMT1/HP1 interactions promoted or enhanced in vivo tumorigenesis in a mouse glioma model...
2013: Clinical Epigenetics
Shinichiro Takahashi
The development of novel technologies, such as massively parallel DNA sequencing, has led to the identification of several novel recurrent gene mutations, such as DNA methyltransferase (Dnmt)3a, ten-eleven-translocation oncogene family member 2 (TET2), isocitrate dehydrogenase (IDH)1/2, additional sex comb-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and ubiquitously transcribed tetratricopeptide repeat X chromosome (UTX) mutations in acute myeloid leukemia (AML) and other myeloid malignancies. These findings strongly suggest a link between recurrent genetic alterations and aberrant epigenetic regulations, resulting from an abnormal DNA methylation and histone modification status...
September 2013: International Journal of Molecular Medicine
Süreyya Bozkurt, Tülin Özkan, Füsun Özmen, Yusuf Baran, Asuman Sunguroğlu, Emin Kansu
In chronic myeloid leukemia (CML), epigenetic modifications such as promoter hypermethylation and inactive histone modification are known mechanisms of drug resistance. In our study, we investigated the roles of promoter hypermethylation of BIM and BID genes and H3K27me3 histone modification on imatinib resistance. We detected higher expression levels of BIM and BID genes and lower expression levels of EZH2, EED2, SIRT1, and SUZ12 genes in imatinib-resistant K562/IMA-3 cells compared to imatinib-non-resistant K562 cells...
July 2013: Hematology (Amsterdam, Netherlands)
Yuka Sugimoto, Mikkael A Sekeres, Hideki Makishima, Fabiola Traina, Valeria Visconte, Anna Jankowska, Andres Jerez, Hadrian Szpurka, Christine L O'Keefe, Kathryn Guinta, Manuel Afable, Ramon Tiu, Kathy L McGraw, Alan F List, Jaroslaw Maciejewski
BACKGROUND: While lenalidomide (LEN) shows high efficacy in myelodysplastic syndromes (MDS) with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. DESIGN AND METHODS: We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML) without del[5q] by metaphase cytogenetics (MC) who underwent therapy with LEN...
March 5, 2012: Journal of Hematology & Oncology
Jie-Yu Wang, Zhi-Jian Xiao
The myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorders. So far, the etiology and pathogenesis of MDS is poorly understood. Recently, more and more epigenetic regulator gene such as TET2, ASXL1, EZH2, DNMT3A and UTX mutations were detected in patients with MDS: TET2 may convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC). TET2 is the most frequently mutated gene in MDS known so far and it may act as tumor-suppressor gene. ASXL1 belongs to the enhancer of trithorax and Polycomb (ETP) gene group...
October 2011: Zhongguo Shi Yan Xue Ye Xue za Zhi
Ah-Young So, Ji-Won Jung, Seunghee Lee, Hyung-Sik Kim, Kyung-Sun Kang
Epigenetic regulation of gene expression is well known mechanism that regulates cellular senescence of cancer cells. Here we show that inhibition of DNA methyltransferases (DNMTs) with 5-azacytidine (5-AzaC) or with specific small interfering RNA (siRNA) against DNMT1 and 3b induced the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) and increased p16(INK4A) and p21(CIP1/WAF1) expression. DNMT inhibition changed histone marks into the active forms and decreased the methylation of CpG islands in the p16(INK4A) and p21(CIP1/WAF1) promoter regions...
May 10, 2011: PloS One
Swarnali Acharyya, Sudarshana M Sharma, Alfred S Cheng, Katherine J Ladner, Wei He, William Kline, Huating Wang, Michael C Ostrowski, Tim H Huang, Denis C Guttridge
BACKGROUND: Classical NF-kappaB signaling functions as a negative regulator of skeletal myogenesis through potentially multiple mechanisms. The inhibitory actions of TNFalpha on skeletal muscle differentiation are mediated in part through sustained NF-kappaB activity. In dystrophic muscles, NF-kappaB activity is compartmentalized to myofibers to inhibit regeneration by limiting the number of myogenic progenitor cells. This regulation coincides with elevated levels of muscle derived TNFalpha that is also under IKKbeta and NF-kappaB control...
August 30, 2010: PloS One
Ruth R E Williams, Véronique Azuara, Pascale Perry, Stephan Sauer, Maria Dvorkina, Helle Jørgensen, Jeffery Roix, Philip McQueen, Tom Misteli, Matthias Merkenschlager, Amanda G Fisher
Determining how genes are epigenetically regulated to ensure their correct spatial and temporal expression during development is key to our understanding of cell lineage commitment. Here we examined epigenetic changes at an important proneural regulator gene Mash1 (Ascl1), as embryonic stem (ES) cells commit to the neural lineage. In ES cells where the Mash1 gene is transcriptionally repressed, the locus replicated late in S phase and was preferentially positioned at the nuclear periphery with other late-replicating genes (Neurod, Sprr2a)...
January 1, 2006: Journal of Cell Science
Emmanuelle Viré, Carmen Brenner, Rachel Deplus, Loïc Blanchon, Mario Fraga, Céline Didelot, Lluis Morey, Aleyde Van Eynde, David Bernard, Jean-Marie Vanderwinden, Mathieu Bollen, Manel Esteller, Luciano Di Croce, Yvan de Launoit, François Fuks
The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA methylation systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 (Enhancer of Zeste homolog 2) interacts-within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)-with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo...
February 16, 2006: Nature
Inmaculada Hernández-Muñoz, Panthea Taghavi, Coenraad Kuijl, Jacques Neefjes, Maarten van Lohuizen
Polycomb group (PcG) proteins are epigenetic chromatin modifiers involved in heritable gene repression. Two main PcG complexes have been characterized. Polycomb repressive complex 2 (PRC2) is thought to be involved in the initiation of gene silencing, whereas Polycomb repressive complex 1 (PRC1) is implicated in the stable maintenance of gene repression. Here, we investigate the kinetic properties of the binding of one of the PRC1 core components, BMI1, with PcG bodies. PcG bodies are unique nuclear structures located on regions of pericentric heterochromatin, found to be the site of accumulation of PcG complexes in different cell lines...
December 2005: Molecular and Cellular Biology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"