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Cancer epigenetics

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https://www.readbyqxmd.com/read/29350283/epigenetic-regulation-of-neuroblastoma-development
#1
REVIEW
Durinck Kaat, Speleman Frank
In recent years, technological advances have enabled a detailed landscaping of the epigenome and the mechanisms of epigenetic regulation that drive normal cell function, development and cancer. Rather than merely a structural entity to support genome compaction, we now look at chromatin as a very dynamic and essential constellation that is actively participating in the tight orchestration of transcriptional regulation as well as DNA replication and repair. The unique feature of chromatin flexibility enabling fast switches towards more or less restricted epigenetic cellular states is, not surprisingly, intimately connected to cancer development and treatment resistance, and the central role of epigenetic alterations in cancer is illustrated by the finding that up to 50% of all mutations across cancer entities affect proteins controlling the chromatin status...
January 19, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29348905/bridging-the-divide-preclinical-research-discrepancies-between-triple-negative-breast-cancer-cell-lines-and-patient-tumors
#2
REVIEW
Andrew Sulaiman, Lisheng Wang
Triple-negative breast cancer (TNBC) is the most refractory subtype of breast cancer and disproportionately accounts for the majority of breast cancer related deaths. Effective treatment of this disease remains an unmet medical need. Over the past several decades, TNBC cell lines have been used as the foundation for drug development and disease modeling. However, ever-mounting research demonstrates striking differences between cell lines and clinical TNBC tumors, disconnecting bench research and actual clinical responses...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348808/dual-nampt-hdac-inhibitors-as-a-new-strategy-for-multitargeting-antitumor-drug-discovery
#3
Wei Chen, Guoqiang Dong, Ying Wu, Wannian Zhang, Chaoyu Miao, Chunquan Sheng
Novel dual nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase (HDAC) inhibitors were designed by a pharmacophore fusion approach. The thiazolocarboxamide inhibitors were highly active for both targets. In particular, compound 7f (NAMPT IC50 = 15 nM, HDAC1 IC50 = 2 nM) showed potent in vivo antitumor efficacy in the HCT116 xenograft model. The study offers a new strategy for multitarget antitumor drug discovery by simultaneously acting on cancer metabolism and epigenetics.
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29346310/ar-signaling-in-human-malignancies-prostate-cancer-and-beyond
#4
EDITORIAL
Emmanuel S Antonarakis
The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer...
January 18, 2018: Cancers
https://www.readbyqxmd.com/read/29344347/epigenetic-alterations-in-tramp-mice-epigenome-dna-methylation-profiling-using-medip-seq
#5
Wenji Li, Ying Huang, Davit Sargsyan, Tin Oo Khor, Yue Guo, Limin Shu, Anne Yuqing Yang, Chengyue Zhang, Ximena Paredes-Gonzalez, Michael Verzi, Ronald P Hart, Ah-Ng Kong
Purpose: We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways. Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq)...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29343995/humanmethylation450k-array-identified-biomarkers-predict-tumour-recurrence-progression-at-initial-diagnosis-of-high-risk-non-muscle-invasive-bladder-cancer
#6
Mark O Kitchen, Richard T Bryan, Richard D Emes, Christopher J Luscombe, K K Cheng, Maurice P Zeegers, Nicholas D James, Lyndon M Gommersall, Anthony A Fryer
Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment...
2018: Biomarkers in Cancer
https://www.readbyqxmd.com/read/29342868/hypoxia-and-hormone-mediated-pathways-converge-at-the-histone-demethylase-kdm4b-in-cancer
#7
REVIEW
Jun Yang, Adrian L Harris, Andrew M Davidoff
Hormones play an important role in pathophysiology. The hormone receptors, such as estrogen receptor alpha and androgen receptor in breast cancer and prostate cancer, are critical to cancer cell proliferation and tumor growth. In this review we focused on the cross-talk between hormone and hypoxia pathways, particularly in breast cancer. We delineated a novel signaling pathway from estrogen receptor to hypoxia-inducible factor 1, and discussed the role of this pathway in endocrine therapy resistance. Further, we discussed the estrogen and hypoxia pathways converging at histone demethylase KDM4B, an important epigenetic modifier in cancer...
January 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341428/epigenetic-silencing-of-tap1-in-aldefluor-breast-cancer-stem-cells-contributes-to-their-enhanced-immune-evasion
#8
Mohammad Sultan, Dejan Vidovic, Arianne S Paine, Thomas T Huynh, Krysta M Coyle, Margaret L Thomas, Brianne M Cruickshank, Cheryl A Dean, Derek R Clements, Youra Kim, Kristin Lee, Shashi A Gujar, Ian C Weaver, Paola Marcato
Avoiding detection and destruction by immune cells is key for tumor initiation and progression. The important role of cancer stem cells (CSC) in tumor initiation has been well established, yet their ability to evade immune detection and targeting is only partly understood. To investigate the ability of breast CSCs to evade immune detection we identified a highly tumorigenic population in a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase (ALDH) activity. We performed tumor growth studies in immunocompetent and immunocompromised mice...
January 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29340905/expression-of-vhl-tumor-suppressor-mrna-and-mir-92a-in-papillary-thyroid-carcinoma-and-their-correlation-with-clinical-and-pathological-parameters
#9
Lidija Todorović, Boban Stanojević, Vesna Mandušić, Nina Petrović, Vladan Živaljević, Ivan Paunović, Aleksandar Diklić, Vladimir Saenko, Shunichi Yamashita
A growing body of evidence suggests a role of the von Hippel-Lindau (VHL) tumor suppressor gene in the progression of papillary thyroid carcinoma (PTC). Our previous study of VHL in PTCs showed that lower VHL expression was associated with aggressive tumor features, but we found no evidence for VHL downregulation through common genetic or epigenetic modifications. Several studies pointed to a role of microRNA-92a (miR-92a) in the regulation of VHL expression in different cancers. In the present study, we examined the expression levels of VHL mRNA and miR-92a in 42 pairs of PTCs and matched non-tumor thyroid tissues by means of quantitative RT-PCR...
January 16, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29340103/anti-neoplastic-drugs-increase-caveolin-1-dependent-migration-invasion-and-metastasis-of-cancer-cells
#10
Natalia I Díaz-Valdivia, Claudia C Calderón, Jorge E Díaz, Lorena Lobos-González, Hugo Sepulveda, Rina J Ortíz, Samuel Martinez, Veronica Silva, Horacio J Maldonado, Patricio Silva, Sergio Wehinger, Verónica A Burzio, Vicente A Torres, Martín Montecino, Lisette Leyton, Andrew F G Quest
Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340089/lncrna-rncr3-promotes-chop-expression-by-sponging-mir-185-5p-during-mdsc-differentiation
#11
Wencong Shang, Zhenzhen Tang, Yunhuan Gao, Houbao Qi, Xiaomin Su, Yuan Zhang, Rongcun Yang
Myeloid-derived suppressor cells (MDSCs) play a critical role in regulating immune responses in cancer and other pathological conditions. Mechanism(s) regulating MDSC differentiation and function is not completely clear, especially epigenetic regulation. In this study, we found that MDSCs express retinal non-coding RNA3 (RNCR3), and the expression in MDSCs is upregulated by inflammatory and tumor associated factors. RNCR3 may function as a competing endogenous RNA (ceRNA) to promote Chop expression by sponging miR-185-5p during MDSC differentiation...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339836/the-role-of-metabolic-enzymes-in-mesenchymal-tumors-and-tumor-syndromes-genetics-pathology-and-molecular-mechanisms
#12
REVIEW
Inga-Marie Schaefer, Jason L Hornick, Judith V M G Bovée
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate...
January 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29339820/histone-variant-macroh2a1-plays-an-isoform-specific-role-in-suppressing-epithelial-mesenchymal-transition
#13
Dayle Q Hodge, Jihong Cui, Matthew J Gamble, Wenjun Guo
Epithelial-Mesenchymal Transition (EMT) is a biological program that plays key roles in various developmental and pathological processes. Although much work has been done on signaling pathways and transcription factors regulating EMT, the epigenetic regulation of EMT remains not well understood. Histone variants have been recognized as a key group of epigenetic regulators. Among them, macroH2A1 is involved in stem cell reprogramming and cancer progression. We postulated that macroH2A1 may play a role in EMT, a process involving reprogramming of cellular states...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339543/genes-predisposed-to-dna-hypermethylation-during-acquired-resistance-to-chemotherapy-are-identified-in-ovarian-tumors-by-bivalent-chromatin-domains-at-initial-diagnosis
#14
Edward Curry, Constanze Zeller, Nahal Masrour, Darren Patten, John Gallon, Charlotte S Wilhelm-Benartzi, Sadaf Ghaem-Maghami, David D L Bowtell, Robert Brown
Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells aberrantly poised genes may facilitate changes in transcriptional states after exposure to anti-cancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3 and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29339538/e6-protein-expressed-by-high-risk-hpv-activates-super-enhancers-of-the-egfr-and-c-met-oncogenes-by-destabilizing-the-histone-demethylase-kdm5c
#15
Xiaohua Chen, Jun Xian Loo, Xin Shi, Wenjun Xiong, Yong Guo, Haiqiang Ke, Mingkun Yang, Yanping Jiang, Siyu Xia, Min Zhao, Shan Zhong, ChunJiang He, Li Fu, Feng Li
The high-risk (HR) human papillomaviruses (HPV) are causative agents of anogenital tract dysplasia and cancers and a fraction of head and neck cancers. The HR HPV E6 oncoprotein possesses canonical oncogenic functions, such as p53 degradation and telomerase activation. It is also capable of stimulating expression of several oncogenes, but the molecular mechanism underlying these events are poorly understood. Here we provide evidence that HPV16 E6 physically interacts with histone H3K4 demethylase KDM5C, resulting in its degradation in an E3 ligase E6AP- and proteasome-dependent manner...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29339473/identification-of-thioredoxin-interacting-protein-txnip-as-a-downstream-target-for-igf1-action
#16
Karthik Nagaraj, Lena Lapkina-Gendler, Rive Sarfstein, David Gurwitz, Metsada Pasmanik-Chor, Zvi Laron, Shoshana Yakar, Haim Werner
Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339244/epigenetics-of-breast-cancer-biology-and-clinical-implication-in-the-era-of-precision-medicine
#17
REVIEW
Barbara Pasculli, Raffaela Barbano, Paola Parrella
In the last years, mortality from breast cancer has declined in western countries as a consequence of a more widespread screening resulting in earlier detection, as well as an improved molecular classification and advances in adjuvant treatment. Nevertheless, approximately one third of breast cancer patients will develop distant metastases and eventually die for the disease. There is now a compelling body of evidence suggesting that epigenetic modifications comprising DNA methylation and chromatin remodeling play a pivotal role since the early stages of breast cancerogenesis...
January 12, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29339153/inhibition-of-cox-2-and-5-lox-regulates-the-progression-of-colorectal-cancer-by-promoting-pten-and-suppressing-pi3k-akt-pathway
#18
Jian Chang, Nan Tang, Qi Fang, Kongfan Zhu, Lei Liu, Xingcheng Xiong, Zhongchao Zhu, Bixiang Zhang, Mingzhi Zhang, Jing Tao
For colorectal cancer (CRC) patients, local and systemic inflammatory responses have been extensively reported to closely associate with patient survival. However, the specific signalling pathways responsible for carcinogenic responses are unclear. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of PI3K/AKT pathway that is gradually inactivated in cancers through mutation, loss of heterozygosity and others epigenetic mechanisms. In addition, COX and LOX metabolic pathways of arachidonic acid (AA) play a crucial role in promoting adenoma development...
January 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29337063/bmi1-activates-wnt-signaling-in-colon-cancer-by-negatively-regulating-the-wnt-antagonist-idax
#19
Feiyue Yu, Chuanyi Zhou, Hui Zeng, Yabing Liu, Shangfu Li
Aberrant activation of Wnt signaling plays a critical role in the development of colon cancer. BMI, a component of the polycomb repressive complex (PRC1), is upregulated in various types of cancer and contributes to epigenetic silencing of tumor suppressors. In this study, we showed that BMI1 is upregulated in colon cancer tissues and cell lines. Overexpression of BMI1 in primary epithelial colon cells promotes cellular growth and activates WNT pathway, while BMI1 silencing in colon cancer cells represses these effects...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29337058/ehmt2-is-a-metastasis-regulator-in-breast-cancer
#20
Kwangho Kim, Mi-Young Son, Cho-Rok Jung, Dae-Soo Kim, Hyun-Soo Cho
Various modes of epigenetic regulation of breast cancer proliferation and metastasis have been investigated, but epigenetic mechanisms involved in breast cancer metastasis remain elusive. Thus, in this study, EHMT2 (a histone methyltransferase) was determined to be significantly overexpressed in breast cancer tissues and in Oncomine data. In addition, knockdown of EHMT2 reduced cell migration/invasion and regulated the expression of EMT-related markers (E-cadherin, Claudin 1, and Vimentin). Furthermore, treatment with BIX-01294, a specific inhibitor of EHMT2, affected migration/invasion in MDA-MB-231 cells...
January 11, 2018: Biochemical and Biophysical Research Communications
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