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Cancer epigenetics

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https://www.readbyqxmd.com/read/28239551/genome-wide-chromatin-accessibility-dna-methylation-and-gene-expression-analysis-of-histone-deacetylase-inhibition-in-triple-negative-breast-cancer
#1
Matias A Bustos, Matthew P Salomon, Nellie Nelson, Sandy C Hsu, Maggie L DiNome, Dave S B Hoon, Diego M Marzese
Triple-negative breast cancer (TNBC), especially the subset with a basal phenotype, represents the most aggressive subtype of breast cancer. Unlike other solid tumors, TNBCs harbor a low number of driver mutations. Conversely, we and others have demonstrated a significant impact of epigenetic alterations, including DNA methylation and histone post-translational modifications, affecting TNBCs. Due to the promising results in pre-clinical studies, histone deacetylase inhibitors (HDACi) are currently being tested in several clinical trials for breast cancer and other solid tumors...
June 2017: Genomics Data
https://www.readbyqxmd.com/read/28238728/an-integrative-transcriptomic-analysis-reveals-bisphenol-a-exposure-induced-dysregulation-of-microrna-expression-in-human-endometrial-cells
#2
Wei-Chun Chou, Pei-Hsuan Lee, Yan-Yan Tan, Ho-Chen Lin, Chung-Wei Yang, Kuan-Hsueh Chen, Chun-Yu Chuang
Bisphenol A (BPA) are commonly used in the manufacture of polycarbonate plastics. Higher BPA exposure levels have been found in patients with endometrial hyperplasia that is one of risk factors of endometrial cancer (EC). Aberrant microRNAs (miRNAs) regulation has been observed in the development of cancer. Thus, this study investigated whether BPA exposure can disrupt miRNA regulation and its gene expression regarding to EC carcinogenic progress. Microarray experiments of miRNA and mRNA were performed in human endometrial cancer RL95-2 cells with treatment of low-to-moderate (10, 10(3) and 10(5)nM) BPA to explore the aberrant genes corresponding to human EC progression...
February 23, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28238718/towards-therapeutic-advances-in-melanoma-management-an-overview
#3
REVIEW
Swarnendra Singh, Atif Zafar, Saman Khan, Imrana Naseem
Melanoma is one of the most aggressive types of skin cancer with rapidly increasing incidence rate. The disease is largely considered incurable and the patients diagnosed with metastatic melanoma have a survival of not more than five years. Despite of the recent advances in anti-melanoma chemo- and immunotherapies, the available drugs are relatively toxic and responsive to only a limited subset of lesions. Currently, topical pharmacotherapy is demonstrated as an effective approach for the treatment of various skin cancers...
February 23, 2017: Life Sciences
https://www.readbyqxmd.com/read/28238060/novel-biotechnology-approaches-in-colorectal-cancer-diagnosis-and-therapy
#4
REVIEW
Soudabeh Kavousipour, Fathemeh Khademi, Mozhdeh Zamani, Bahareh Vakili, Pooneh Mokarram
With ever-increasing molecular information about colorectal cancer (CRC), there is an expectation to detect more sensitive and specific molecular markers for new advanced diagnostic methods that can surpass the limitations of current screening tests. Moreover, enhanced molecular pathology knowledge about cancer has led to the development of targeted therapies, designed to interfere with specific aberrant biological pathways in cancer. Furthermore, biotechnology has opened a new window in CRC diagnosis and treatment by introducing different application of antibodies, antibody fragments, non-Ig scaffold proteins, and aptamers in targeted therapy and drug delivery...
February 25, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28235630/comprehensive-immunohistochemical-analysis-of-histone-deacetylases-in-pancreatic-neuroendocrine-tumors-hdac5-as-a-predictor-of-poor-clinical-outcome
#5
Eckhard Klieser, Romana Urbas, Stefan Stättner, Florian Primavesi, Tarkan Jäger, Adam Dinnewitzer, Christian Mayr, Tobias Kiesslich, Klaus Holzmann, Pietro Di Fazio, Daniel Neureiter, Stefan Swierczynski
Epigenetic factors contribute to carcinogenesis, tumor promotion and chemoresistance. Histone deacetylases (HDACs) are epigenetic regulators that primarily cause chromatin compaction, leading to inaccessibility of promoter regions and eventually gene silencing. Many cancer entities feature over-expression of HDACs. Currently, the role of HDACs in pancreatic neuroendocrine tumors (pNETs) is unclear. We analyzed expression patterns of all HDAC classes (Class I, IIA, IIB, III & IV) in five human tissue microarrays (TMA) representing 57 pNETs resected between 1997 and 2013 and corresponding control tissue...
February 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28235401/expression-of-socs1-and-the-downstream-targets-of-its-putative-tumor-suppressor-functions-in-prostate-cancer
#6
Martin Chevrier, Diwakar Bobbala, Alberto Villalobos-Hernandez, Md Gulam Musawwir Khan, Sheela Ramanathan, Caroline Saucier, Gerardo Ferbeyre, Sameh Geha, Subburaj Ilangumaran
BACKGROUND: Suppressor of cytokine signaling 1 (SOCS1) is considered a tumor suppressor due to frequent epigenetic and micro-RNA-mediated repression of its gene expression in diverse cancers. In prostate cancer (PCa), elevated expression of miR-30d that targets SOCS1 mRNA is associated with increased risk of disease recurrence. SOCS1 can mediate its tumor suppressor functions by diverse mechanisms such as inhibiting the JAK-STAT signaling pathway, promoting the tumor suppressor functions of p53, attenuating MET receptor tyrosine kinase signaling and blocking the oncogenic potential of the cell cycle inhibitor p21(CIP1) (p21)...
February 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28235398/testis-specific-y-like-5-gene-expression-methylation-and-implications-for-drug-sensitivity-in-prostate-carcinoma
#7
Senthil R Kumar, Jeffrey N Bryan, Magda Esebua, James Amos-Landgraf, Tanner J May
BACKGROUND: TSPYL5, a putative tumor suppressor gene, belongs to the nucleosome assembly protein family. The chromosomal location of the TSPYL5 gene is 8Q22.1, and its exact role in prostate cancer etiology remains unclear. Further TSPYL5 gene and protein expression in prostate carcinoma cells and diseased tissues including its susceptibility for epigenetic silencing is unknown. Also, not known is the variation in TSPYL5 protein expression with regards to progression of prostatic carcinoma and its possible role in drug sensitivity...
February 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28231576/molecular-markers-involved-in-tumorigenesis-of-thyroid-carcinoma-focus-on-aggressive-histotypes
#8
Gustavo C Penna, Fernanda Vaisman, Mario Vaisman, Manuel Sobrinho-Simões, Paula Soares
Thyroid cancer derived from follicular cells (TCDFC) comprises well-differentiated (papillary and follicular) carcinoma, poorly differentiated carcinoma, and anaplastic carcinoma. Papillary thyroid carcinoma is the most common endocrine cancer, and its incidence is steadily increasing. Lethality and aggressiveness of TCDFC is inversely correlated with differentiation degree. In this review, an emphasis has been put on molecular markers involved in tumorigenesis of thyroid carcinoma with a focus on aggressive histotypes and the role of such biomarkers in predicting thyroid cancer outcome...
February 24, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28230864/dicer-promotes-tumorigenesis-by-translocating-to-nucleus-to-promote-sfrp1-promoter-methylation-in-cholangiocarcinoma-cells
#9
Wenlong Cheng, Yongqiang Qi, Li Tian, Bing Wang, Wenhua Huang, Yongjun Chen
Dicer, a member of the RNase III family of endoribonucleases, has an important role in regulating methylation of CpG islands in mammal cancer cells. However, the underlying mechanism of action remains unclear. In this study, we demonstrated that upregulation of Dicer in cholangiocarcinoma (CCA) cells and its translocation to nuclues to interact with heterochromatin protein 1α (HP1α). The nuclear Dicer/HP1α complex appeared to promote both H3K9 trimethylation and DNA methylation of the secreted frizzled-related protein 1 (SFRP1) promoter...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28229117/dna-methylation-data-for-identification-of-epigenetic-targets-of-resveratrol-in-triple-negative-breast-cancer-cells
#10
Rubiceli Medina-Aguilar, Carlos Pérez-Plasencia, Patricio Gariglio, Laurence A Marchat, Ali Flores-Pérez, César López-Camarillo, Jaime García Mena
Previous studies revealed that some bioactive food components have anti-cancer effects. However epigenetic effects of dietary compound resveratrol are largely unknown in breast cancer cells (M.A. Dawson, T. Kouzarides, 2012) [1]. Here we provide novel data and comparisons of DNA methylation status of promoter gene regions in response to resveratrol treatment at 24 h and 48 h versus untreated MDA-MB-231 breast cancer cells. DNA methylation changes were measured using Array-PRIMES method (aPRIMES) followed by whole-genome hybridization using human DNA methylation promoter microarray NimbleGen HG18 Refseq Promoter 3×720 K array...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#11
Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov
BACKGROUND: Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28225782/chronic-treatment-of-non-small-cell-lung-cancer-cells-with-gefitinib-leads-to-an-epigenetic-loss-of-epithelial-properties-associated-with-reductions-in-microrna-155-and-200c
#12
Michiko Narita, Eri Shimura, Atsumi Nagasawa, Toshiki Aiuchi, Yukari Suda, Yusuke Hamada, Daigo Ikegami, Chizuru Iwasawa, Kazuhiko Arakawa, Katsuhide Igarashi, Naoko Kuzumaki, Yusuke Yoshioka, Takahiro Ochiya, Hideyuki Takeshima, Toshikazu Ushijima, Minoru Narita
BACKGROUND: The EGFR tyrosine kinase inhibitor gefitinib is used in therapy for non-small-cell lung cancer (NSCLC). However, its application is limited by resistance-accelerated disease progression, which is accompanied by the epithelial-to-mesenchymal transition (EMT). In the present study, we performed multiple expression analyses of microRNAs (miRNAs) and quantified the expression of several related EMT players in gefitinib-resistant NSCLC cells. METHODS AND RESULTS: To establish gefitinib-resistant NSCLC cells, gefitinib-sensitive HCC827 cells, which exhibit an in-frame deletion [E746-A750] in EGFR exon 19, were exposed to gefitinib for at least 1...
2017: PloS One
https://www.readbyqxmd.com/read/28225755/intragenic-dna-methylation-prevents-spurious-transcription-initiation
#13
Francesco Neri, Stefania Rapelli, Anna Krepelova, Danny Incarnato, Caterina Parlato, Giulia Basile, Mara Maldotti, Francesca Anselmi, Salvatore Oliviero
In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that this Dnmt3b function is dependent on its enzymatic activity and recruitment to the gene body by H3K36me3...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28225433/the-role-of-5-hydroxymethylcytosine-in-melanoma
#14
Feng-Juan Li, Li-Ming Li, Rui-Hua Zhang, Cui Xu, Pan Zhou, Jia Long, Gang Hu, Ming-Jun Jiang
Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation...
February 20, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28225000/carcinogenesis-and-therapeutics-the-microbiota-perspective
#15
REVIEW
Matthew C B Tsilimigras, Anthony Fodor, Christian Jobin
Cancer arises from the acquisition of multiple genetic and epigenetic changes in host cells over the span of many years, promoting oncogenic traits and carcinogenesis. Most cancers develop following random somatic alterations of key oncogenic genes, which are favoured by a number of risk factors, including lifestyle, diet and inflammation. Importantly, the environment where tumours evolve provides a unique source of signalling cues that affects cancer cell growth, survival, movement and metastasis. Recently, there has been increased interest in how the microbiota, the collection of microorganisms inhabiting the host body surface and cavities, shapes a micro-environment for host cells that can either promote or prevent cancer formation...
February 22, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28223039/oncogene-lsd1-is-epigenetically-suppressed-by-mir-137-overexpression-in-human-non-small-cell-lung-cancer
#16
Xin Zhang, Xiujuan Zhang, Bo Yu, Rongpeng Hu, Lanxiang Hao
PURPOSE: We examined the epigenetic regulation of microRNA-137 (miR-137) on lysine-specific demethylase 1 (KDM1A, or LSD1) induced oncogenic effects in NSCLC. METHODS: NSCLC cell lines, A549 and H460 cells were transfected with a mammalian LSD1 overexpression plasmid. It's effects on endogenous KDM1A gene and LSD1 protein expressions were examined by qRT-PCR and western blot assays. NSCLC proliferation and migration were also examined by MTT proliferation and wound-scratch assays, respectively...
February 18, 2017: Biochimie
https://www.readbyqxmd.com/read/28222791/epig-statistical-inference-and-profiling-of-dna-methylation-from-whole-genome-bisulfite-sequencing-data
#17
Martin Vincent, Kamilla Mundbjerg, Jakob Skou Pedersen, Gangning Liang, Peter A Jones, Torben Falck Ørntoft, Karina Dalsgaard Sørensen, Carsten Wiuf
The study of epigenetic heterogeneity at the level of individual cells and in whole populations is the key to understanding cellular differentiation, organismal development, and the evolution of cancer. We develop a statistical method, epiG, to infer and differentiate between different epi-allelic haplotypes, annotated with CpG methylation status and DNA polymorphisms, from whole-genome bisulfite sequencing data, and nucleosome occupancy from NOMe-seq data. We demonstrate the capabilities of the method by inferring allele-specific methylation and nucleosome occupancy in cell lines, and colon and tumor samples, and by benchmarking the method against independent experimental data...
February 21, 2017: Genome Biology
https://www.readbyqxmd.com/read/28222671/reversal-of-hypermethylation-and-reactivation-of-glutathione-s-transferase-pi-1-gene-by-curcumin-in-breast-cancer-cell-line
#18
Umesh Kumar, Ujjawal Sharma, Garima Rathi
One of the mechanisms for epigenetic silencing of tumor suppressor genes is hypermethylation of cytosine residue at CpG islands at their promoter region that contributes to malignant progression of tumor. Therefore, activation of tumor suppressor genes that have been silenced by promoter methylation is considered to be very attractive molecular target for cancer therapy. Epigenetic silencing of glutathione S-transferase pi 1, a tumor suppressor gene, is involved in various types of cancers including breast cancer...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28220843/dusp1-promoter-methylation-in-peripheral-blood-leukocyte-is-associated-with-triple-negative-breast-cancer-risk
#19
Jing Li, Yanbo Chen, Hongyuan Yu, Jingshen Tian, Fengshun Yuan, Jialong Fan, Yupeng Liu, Lin Zhu, Fan Wang, Yashuang Zhao, Da Pang
DNA methylation is one of the most common epigenetic alterations, providing important information regarding cancer risk and prognosis. A case-control study (423 breast cancer cases, 509 controls) and a case-only study (326 cases) were conducted to evaluate the association of DUSP1 promoter methylation with breast cancer risk and clinicopathological characteristics. No significant association between DUSP1 methylation in peripheral blood leukocyte (PBL) DNA and breast cancer risk was observed. DUSP1 methylation was significantly associated with ER/PR-negative status; in particular, triple-negative breast cancer patients showed the highest frequency of DUSP1 methylation in both tumour DNA and PBL DNA...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#20
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
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