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Cancer epigenetics

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https://www.readbyqxmd.com/read/28326594/hypoacetylation-of-acetyl-histone-h3-h3k9ac-as-marker-of-poor-prognosis-in-oral-cancer
#1
Liana Preto Webber, Vivian Petersen Wagner, Marina Curra, Pablo Agustin Vargas, Luise Meurer, Vinícius Coelho Carrard, Cristiane Helena Squarize, Rogério Moraes Castilho, Manoela Domingues Martins
AIMS: Epigenetics refers to changes in cell characteristics that occur independently of modifications to the DNA sequence. Oral carcinogenesis is influenced by modifications in epigenetic mechanisms, including changes in histones, which are proteins that support chromatin remodeling for the dynamic regulation of gene expression and silencing. The dysregulation of histone acetylation can lead to the uncontrolled activity of different genes, thereby triggering events associated with malignant transformation...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28326191/global-histone-modification-fingerprinting-in-human-cells-using-epigenetic-reverse-phase-protein-array
#2
Marina Partolina, Hazel C Thoms, Kenneth G MacLeod, Giovanny Rodriguez-Blanco, Matthew N Clarke, Anuroop V Venkatasubramani, Rima Beesoo, Vladimir Larionov, Vidushi S Neergheen-Bhujun, Bryan Serrels, Hiroshi Kimura, Neil O Carragher, Alexander Kagansky
The balance between acetylation and deacetylation of histone proteins plays a critical role in the regulation of genomic functions. Aberrations in global levels of histone modifications are linked to carcinogenesis and are currently the focus of intense scrutiny and translational research investments to develop new therapies, which can modify complex disease pathophysiology through epigenetic control. However, despite significant progress in our understanding of the molecular mechanisms of epigenetic machinery in various genomic contexts and cell types, the links between epigenetic modifications and cellular phenotypes are far from being clear...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28325946/epigenetically-regulated-fibronectin-leucine-rich-transmembrane-protein-2-flrt2-shows-tumor-suppressor-activity-in-breast-cancer-cells
#3
Hansol Bae, Byungtak Kim, Hyunkyung Lee, Seungyeon Lee, Han-Sung Kang, Sun Jung Kim
To identify dysregulated genes by abnormal methylation and expression in breast cancer, we genome-wide analyzed methylation and expression microarray data from the Gene Expression Omnibus and the Cancer Genome Atlas database. One of the genes screened in silico, FLRT2, showed hypermethylation and downregulation in the cancer dataset and the association was verified both in cultured cell lines and cancer patients' tissue. To investigate the role of FLRT2 in breast cancer, its expression was knocked down and upregulated in mammary cell lines, and the effect was examined through three levels of approach: pathway analysis; cell activities such as proliferation, colony formation, migration, and adhesion; target gene expression...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325086/application-of-bacterial-reverse-mutation-assay-for-detection-of-non-genotoxic-carcinogens
#4
Rewan Kanode, Saurabh Chandra, Sharad Sharma
Non-genotoxic carcinogens may play a significant role in development of cancer. Currently short-term assays for mutagenicity classify genotoxic carcinogens and lack the abilities to detect epigenetic carcinogens. The need to develop an endpoint always remains to recognize potentially carcinogenic agents employing rapid and practical bioassays. For this, the present study utilized TA98 and TA1537 tester strains of Salmonella typhimurium to evaluate four non-genotoxic carcinogenic agents (Coumarin, β-Myrcene, Bis(2-ethylhexyl) phthalate and trans-anethole)...
March 22, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#5
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28323900/long-term-exposure-to-estrogen-enhances-chemotherapeutic-efficacy-potentially-through-epigenetic-mechanism-in-human-breast-cancer-cells
#6
Yu-Wei Chang, Kamaleshwar P Singh
Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2) on the efficacy of chemotherapeutic drugs in breast cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28322996/assessing-the-mirna-sponge-potential-of-runx1t1-in-t-8-21-acute-myeloid-leukemia
#7
Alexander Junge, Roza Zandi, Jakob Hull Havgaard, Jan Gorodkin, Jack Bernard Cowland
t(8;21) acute myeloid leukemia (AML) is characterized by a translocation between chromosomes 8 and 21 and formation of a distinctive RUNX1-RUNX1T1 fusion transcript. This translocation places RUNX1T1 under control of the RUNX1 promoter leading to a pronounced upregulation of RUNX1T1 transcripts in t(8;21) AML, compared to normal hematopoietic cells. We investigated the role of highly-upregulated RUNX1T1 under the hypothesis that it acts as competing endogenous RNA (ceRNA) titrating microRNAs (miRNAs) away from their target transcripts and thus contributes to AML formation...
March 16, 2017: Gene
https://www.readbyqxmd.com/read/28320962/genetic-disruption-of-oncogenic-kras-sensitizes-lung-cancer-cells-to-fas-receptor-mediated-apoptosis
#8
Haiwei Mou, Jill Moore, Sunil K Malonia, Yingxiang Li, Deniz M Ozata, Soren Hough, Chun-Qing Song, Jordan L Smith, Andrew Fischer, Zhiping Weng, Michael R Green, Wen Xue
Genetic lesions that activate KRAS account for ∼30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras Here, we show that tumor cells can survive knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320778/the-epitranscriptome-of-noncoding-rnas-in-cancer
#9
REVIEW
Manel Esteller, Pier Paolo Pandolfi
The activity of RNA is controlled by different types of post-transcriptional modifications, such as the addition of methyl groups and other chemical and structural changes, that have been recently described in human cells by high-throughput sequencing. Herein, we will discuss how the so-called epitranscriptome is disrupted in cancer and what the contribution of its writers, readers, and erasers to the process of cellular transformation is, particularly focusing on the epigenetic modifications of ncRNAs.Significance: Chemical modifications of RNA play a central role in the control of messenger and ncRNA activity and, thus, are tightly regulated in cells...
March 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28319413/aberrant-promoter-hypermethylation-of-p16-survivin-and-retinoblastoma-in-gastric-cancer
#10
L Guo, C Huang, Q J Ji
BACKGROUND: Gastric cancer is common and can be found throughout the world. Notoriously like other cancers, gastric cancer is a consequence of cellular regulation disorder. Epigenetics, including many oncogenes or tumour suppressor genes, can provide some clues for this kind of disorder. DNA methylation, especially promoter methylation, which causes the silence/decrease of tumour related genes, has become a focus in various tumour types. The aim of this study was to investigate promoter methylation of certain genes: p16, survivin, retinoblastoma (Rb), all of which have been regarded as genes related to gastric cancer...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28319045/akt-mediated-stabilization-of-histone-methyltransferase-whsc1-promotes-prostate-cancer-metastasis
#11
Ni Li, Wei Xue, Huairui Yuan, Baijun Dong, Yufeng Ding, Yongfeng Liu, Min Jiang, Shan Kan, Tongyu Sun, Jiale Ren, Qiang Pan, Xiang Li, Peiyuan Zhang, Guohong Hu, Yan Wang, Xiaoming Wang, Qintong Li, Jun Qin
Loss of phosphatase and tensin homolog (PTEN) and activation of the PI3K/AKT signaling pathway are hallmarks of prostate cancer (PCa). However, these alterations alone are insufficient for cells to acquire metastatic traits. Here, we have shown that the histone dimethyl transferase WHSC1 critically drives indolent PTEN-null tumors to become metastatic PCa. In a PTEN-null murine PCa model, WHSC1 overexpression in prostate epithelium cooperated with Pten deletion to produce a metastasis-prone tumor. Conversely, genetic ablation of Whsc1 prevented tumor progression in PTEN-null mice...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318385/arsenic-induced-sumoylation-of-mus81-is-involved-in-regulating-genomic-stability
#12
Liyan Hu, Feikun Yang, Lou Lu, Wei Dai
Chronic environmental exposure to metal toxicants such as chromium and arsenic is closely related to the development of several types of common cancers. Genetic and epigenetic studies in the past decade reveal that post-translational modifications of histones play a role in metal carcinogenesis. However, exact molecular mechanisms of metal carcinogenesis remain to be elucidated. In this study we found that As2O3, an environmental metal toxicant, up-regulated overall modifications of many cellular proteins by SUMO2/3...
March 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#13
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315714/cadmium-induced-malignant-transformation-of-rat-liver-cells-potential-key-role-and-regulatory-mechanism-of-altered-apolipoprotein-e-expression-in-enhanced-invasiveness
#14
Masayo Suzuki, Shuso Takeda, Noriko Teraoka-Nishitani, Akane Yamagata, Takahiro Tanaka, Marika Sasaki, Natsuki Yasuda, Makiko Oda, Tatsuji Okano, Kazuhiro Yamahira, Yuta Nakamura, Takanobu Kobayashi, Katsuhito Kino, Hiroshi Miyazawa, Michael P Waalkes, Masufumi Takiguchi
Cadmium is a transition metal that is classified as human carcinogen by the International Agency for Research on Cancer (IARC) with multiple target sites. Many studies using various model systems provide evidence of cadmium-induced malignancy formation in vivo or malignant cell transformation in vitro. Nonetheless, further studies are needed to completely understand the mechanisms of cadmium carcinogenicity. Our prior studies have utilized a rat liver epithelial cell line (TRL 1215) as a model for cadmium-induced malignant transformation...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28315378/epigenetic-regulation-of-ret-receptor-tyrosine-kinase-and-non-coding-rnas-in-mtc
#15
Lauren Jin Suk Joo, Jing Ting Zhao, Matti L Gild, Anthony R Glover, Stan B Sidhu
Medullary thyroid carcinoma (MTC) is an aggressive and rare cancer with limited treatment options for metastatic disease. Due to this, there is a need for a better understanding of MTC biology in the hope of improved treatments. One area of improved understanding of cancer biology is epigenetics. Epigenetics is defined as cellular processes which alter gene expression independent of changes in the primary DNA sequence. These processes include modifications such as DNA methylation, microRNA deregulation and post-translational histone modifications, all of which have been implicated in tumorigenesis of MTC...
March 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28315368/the-emerging-role-of-pi3k-akt-mediated-epigenetic-regulation-in-cancer
#16
REVIEW
Jennifer M Spangle, Thomas M Roberts, Jean J Zhao
The PI3-kinase/AKT pathway integrates signals from external cellular stimuli to regulate essential cellular functions, and is frequently aberrantly activated in human cancers. Recent research demonstrates that tight regulation of the epigenome is critical in preserving and restricting transcriptional activation, which can impact cellular growth and proliferation. In this review we examine mechanisms by which the PI3K/AKT pathway regulates the epigenome to promote oncogenesis, and highlight how connections between PI3K/AKT and the epigenome may impact the future therapeutic treatment of cancers featuring a hyperactivated PI3K/AKT pathway...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315155/synchronous-triple-primary-cancers-of-the-pharynx-and-esophagus
#17
Seita Kataoka, Masami Omae, Yusuke Horiuchi, Akiyoshi Ishiyama, Toshiyuki Yoshio, Toshiaki Hirasawa, Yorimasa Yamamoto, Tomohiro Tsuchida, Junko Fujisaki, Kazuhiko Yamada, Masahiro Igarashi
A 72-year-old male with nausea and heartburn was found to have early pharyngeal squamous cell carcinoma, superficial and advanced esophageal squamous cell carcinoma and early esophageal adenocarcinoma by esophagogastroduodenoscopy. Computerized tomography demonstrated left cardiac lymph node swellings. We prioritized the treatment for esophageal squamous cell carcinoma, as this was the most advanced cancer among the triple primaries. The patient underwent neoadjuvant chemotherapy for esophageal squamous cell carcinoma followed by esophagectomy...
March 17, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28315153/effects-of-histone-deacetylase-inhibitory-prodrugs-on-epigenetic-changes-and-dna-damage-response-in-tumor-and-heart-of-glioblastoma-xenograft
#18
Nataly Tarasenko, Abraham Nudelman, Gabriela Rozic, Suzanne M Cutts, Ada Rephaeli
The histone deacetylase (HDAC) inhibitory prodrugs of butyric (AN7) and valproic (AN446) acids, which release the active acids upon metabolic degradation, were studied examining their differential effects on the viability, HDAC inhibitory activity and the DNA damage response (DDR), in glioblastoma cell and normal human astrocytes (NHAs). In xenografts of glioblastoma, AN7 or AN446 given or the combination of each of them with Dox augmented the anticancer activity of Dox and protected the heart from its toxicity...
March 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28314692/identification-of-an-atypical-etiological-head-and-neck-squamous-carcinoma-subtype-featuring-the-cpg-island-methylator-phenotype
#19
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/28314406/the-role-of-targeted-therapy-in-the-management-of-sinonasal-malignancies
#20
REVIEW
Lawrence Kashat, Christopher H Le, Alexander G Chiu
Cancers develop secondary to genetic and epigenetic changes that provide the cell with a survival advantage that promotes cellular immortality. Malignancy arises when tumors use mechanisms to evade detection and destruction by the immune system. Many malignancies seem to elicit an immune response, yet somehow manage to avoid destruction by the cells of the immune system. Cancers may evade this immune response by numerous mechanisms. Several targeted immune therapies are available that block some of these inhibitory signals and enhance the cell-mediated immune response...
April 2017: Otolaryngologic Clinics of North America
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