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Cancer epigenetics

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https://www.readbyqxmd.com/read/28454418/epigenetic-silencing-of-protocadherin-10-in-colorectal-cancer
#1
Xian Zhong, Hong Shen, Jianshan Mao, Jiawei Zhang, Weidong Han
Colorectal cancer (CRC) is one of the most common types of malignant tumor in the world and occurs through a multi-step process resulting from the accumulation of genetic and epigenetic alterations of the genome. Although the molecular mechanisms of the pathogenesis of CRC remain unclear, the inactivation of tumor suppressor genes (TSGs) through promoter methylation serves an important role. Aberrant methylation is a well-defined marker of CRC. At present, the epigenetic silencing of protocadherin 10 (PCDH10) has been identified as an important TSG with key roles in colorectal carcinogenesis, invasion and metastasis as a frequent and early event...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454353/prmt8-demonstrates-variant-specific-expression-in-cancer-cells-and-correlates-with-patient-survival-in-breast-ovarian-and-gastric-cancer
#2
Sarah J Hernandez, David M Dolivo, Tanja Dominko
Recent emphasis has been placed on the role of epigenetic regulators and epigenetic marks as biomarkers for cancer diagnosis and prognosis, and as therapeutic targets for treatment. One such class of regulators is the protein arginine methyltransferase (PRMT) family. The present study examined available curated data regarding the expression and alteration of one of the least studied PRMT family members, PRMT8, in various types of cancer and cancer cell lines. Publicly available cancer data on PRMT8 expression were examined using the Human Protein Atlas and the Kaplan-Meier Plotter, and reverse transcription-polymerase chain reaction was used to screen a selection of human cell lines for variant-specific PRMT8 expression...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454214/genome-wide-analysis-of-gynecologic-cancer-the-cancer-genome-atlas-in-ovarian-and-endometrial-cancer
#3
Moito Iijima, Kouji Banno, Ryuichiro Okawa, Megumi Yanokura, Miho Iida, Takashi Takeda, Haruko Kunitomi-Irie, Masataka Adachi, Kanako Nakamura, Kiyoko Umene, Yuya Nogami, Kenta Masuda, Eiichiro Tominaga, Daisuke Aoki
Cancer typically develops due to genetic abnormalities, but a single gene abnormality cannot completely account for the onset of cancer. The Cancer Genome Atlas (CGA) project was conducted for the cross-sectional genome-wide analysis of numerous genetic abnormalities in various types of cancer. This approach has facilitated the identification of novel AT-rich interaction domain 1A gene mutations in ovarian clear cell carcinoma, frequent tumor protein 53 (TP53) gene mutations in high-grade ovarian serous carcinoma, and Kirsten rat sarcoma and B-rapidly accelerated fibrosarcoma proto-oncogene, serine/threonine kinase gene mutations in low-grade ovarian serous carcinoma...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454212/reciprocal-regulation-between-micrornas-and-epigenetic-machinery-in-colorectal-cancer
#4
Feng Wang, Yanlei Ma, Huamin Wang, Huanlong Qin
Epigenetics encompasses changes in DNA methylation, histone and chromatin structure, and non-coding RNAs, specifically microRNA (miRNA) expression. Recent advances in the rapidly evolving field of colorectal cancer (CRC) epigenetics have revealed a complicated network of reciprocal interconnections between miRNAs and other epigenetic machinery. On the one hand, miRNA expression may be regulated by epigenetic mechanisms including DNA methylation and histone modifications. However, miRNAs may affect the epigenetic machinery by directly targeting its enzymatic components...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453505/breast-cancer-intra-tumor-heterogeneity-one-tumor-different-entities
#5
José Esparza-López, Elizabet Escobar-Arriaga, Santos Soto-Germes, María de Jesús Ibarra-Sánchez
In recent years, it has become evident that intra-tumor heterogeneity of breast cancer is a big challenge for the diagnosis, treatment, and clinical course of tumor-bearing patients. The advances in molecular biology and other technologies have led to the knowledge that a breast cancer tumor is comprised of multiple cellular entities. Here we review the two theories that have been described, trying to explain the origin of intra-tumor heterogeneity: clonal evolution and cancer stem cells. The first one considers that a single cell gives rise to many subpopulations through the accumulation of multiple aberrations, while the cancer stem cells theory foresees a hierarchical tumor evolution where only a few cells with self-renewal capacity give rise to different subpopulations...
March 2017: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
https://www.readbyqxmd.com/read/28453456/the-synergic-effect-of-hpv-infection-and-epigenetic-anomaly-of-the-p16-gene-in-the-development-of-cervical-cancer
#6
Arif Ahmad, Mohammad Raish, Mohammad Shahid, Swaraj Batra, Vineeta Batra, Syed Akhtar Husain
BACKGROUND: Cervical cancer is the most common cancer in Indian women. Infection with a high-risk human papillomavirus (HR-HPV) is the greatest risk factor for developing cervical cancer. The genetic and epigenetic changes in the tumor suppressor p16 gene is play an important role in the development of cervical cancer. OBJECTIVE: To evaluate the expression and promoter methylation of p16 gene in HR-HPV infected squamous cell carcinoma of the uterine cervix. METHODS: To find out p16INK4a expression and methylation status 105 squamous cell carcinoma of the uterine cervix were investigated by using immunohistochemistry and Methylation Specific PCR techniques...
April 14, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28453394/expression-of-mir-23a-by-apoptotic-regulators-in-human-cancer-a-review
#7
Rabih Roufayel, Seifedine Kadry
MicroRNAs play fundamental roles in mammalian development, differentiation and cellular homeostasis by regulating essential processes such as proliferation, migration, metabolism, migration and cell death. These small non-coding RNAs are also responsible in RNA silencing, and in many developmental and pathological processes. Not surprisingly, miR-23a misexpression contributes to numerous diseases including cancer where certain miRNA genes have been classified as either oncogenes or tumor suppressor genes. Since a single microRNA is capable of targeting a large number of mRNA sequences, de-regulated miRNA expression has the ability to alter various transcripts and activate a wide range of cancer-related pathways...
April 28, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28449010/excess-of-a-rassf1-targeting-microrna-mir-193a-3p-perturbs-cell-division-fidelity
#8
Sofia Pruikkonen, Marko J Kallio
BACKGROUND: Several microRNA (miRNA) molecules have emerged as important post-transcriptional regulators of tumour suppressor and oncogene expression. Ras association domain family member 1 (RASSF1) is a critical tumour suppressor that controls multiple aspects of cell proliferation such as cell cycle, cell division and apoptosis. The expression of RASSF1 is lost in a variety of cancers due to the promoter hypermethylation. METHODS: miR-193a-3p was identified as a RASSF1-targeting miRNA by a dual screening approach...
April 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28448736/orphan-cpg-islands-define-a-novel-class-of-highly-active-enhancers
#9
Joshua S K Bell, Paula M Vertino
CpG islands (CGI) are critical genomic regulatory elements that support transcriptional initiation and are associated with the promoters of most human genes. CGI are distinguished from the bulk genome by their high CpG density, lack of DNA methylation, and euchromatic features. While CGI are canonically known as strong promoters, thousands of 'orphan' CGI lie far from any known transcript, leaving their function an open question. We undertook a comprehensive analysis of the epigenetic state of orphan CGI across over 100 cell types...
April 27, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28447336/review-of-recent-molecular-landscape-knowledge-of-gastric-cancer
#10
REVIEW
Dai Shimizu, Mitsuro Kanda, Yasuhiro Kodera
Gastric cancer (GC) is one of the most frequently diagnosed cancers worldwide and its prognosis remains dismal. One reason for poor outcomes of GC patients is that most are diagnosed when the cancer has already advanced. Novel biomarkers with high sensitivity and specificity are needed to diagnose GC in the early stage. In addition, to improve the outcome of patients with GC, patient stratification according to prognostic factors and sensitivity to chemo(radio)therapy are necessary. Appropriate follow-up criteria and individualized treatment will contribute to improvement in prognosis...
April 27, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28447025/metabolic-cooperation-and-competition-in-the-tumor-microenvironment-implications-for-therapy
#11
REVIEW
Seema Gupta, Amrita Roy, Bilikere S Dwarakanath
The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28446596/dicer-loss-and-recovery-induce-an-oncogenic-switch-driven-by-transcriptional-activation-of-the-oncofetal-imp1-3-family
#12
Courtney K JnBaptiste, Allan M Gurtan, Kevin K Thai, Victoria Lu, Arjun Bhutkar, Mei-Ju Su, Asaf Rotem, Tyler Jacks, Phillip A Sharp
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression critical for organismal viability. Changes in miRNA activity are common in cancer, but how these changes relate to subsequent alterations in transcription and the process of tumorigenesis is not well understood. Here, we report a deep transcriptional, oncogenic network regulated by miRNAs. We present analysis of the gene expression and phenotypic changes associated with global miRNA restoration in miRNA-deficient fibroblasts. This analysis uncovers a miRNA-repressed network containing oncofetal genes Imp1, Imp2, and Imp3 (Imp1-3) that is up-regulated primarily transcriptionally >100-fold upon Dicer loss and is resistant to resilencing by complete restoration of miRNA activity...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28446439/pax3-foxo1-establishes-myogenic-super-enhancers-and-confers-bet-bromodomain-vulnerability
#13
Berkley E Gryder, Marielle E Yohe, Hsien-Chao Chou, Xiaohu Zhang, Joana Marques, Marco Wachtel, Beat Schaefer, Nirmalya Sen, Young K Song, Alberto Gualtieri, Silvia Pomella, Rossella Rota, Abigail Cleveland, Xinyu Wen, Sivasish Sindiri, Jun S Wei, Frederic G Barr, Sudipto Das, Thorkell Andresson, Rajarshi Guha, Madhu Lal-Nag, Marc Ferrer, Jack F Shern, Keji Zhao, Craig J Thomas, Javed Khan
Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and adolescent young adults, driven primarily by the chimeric transcription factor PAX3-FOXO1 (P3F). The mechanisms by which P3F dysregulates chromatin are unknown. We find P3F reprograms the cis-regulatory landscape by inducing (de novo) super enhancers (SEs). P3F uses SEs to setup auto-regulatory loops in collaboration with master transcription factors MYOG, MYOD and MYCN. This myogenic SE circuitry is consistent across cell lines and primary tumors...
April 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#14
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445481/hypomethylating-agents-synergize-with-irinotecan-to-improve-response-to-chemotherapy-in-colorectal-cancer-cells
#15
Anup Sharma, Rajita Vatapalli, Eihab Abdelfatah, K Wyatt McMahon, Zachary Kerner, Angela A Guzzetta, Jasvinder Singh, Cynthia Zahnow, Stephen B Baylin, Sashidhar Yerram, Yue Hu, Nilofer Azad, Nita Ahuja
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA) in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28444545/erratum-to-braf-kras-and-helicobacter-pylori-epigenetic-changes-associated-chronic-gastritis-in-egyptian-patients-with-and-without-gastric-cancer
#16
Dina Sabry, Rasha Ahmed, Sayed Abdalla, Wael Fathy, Ahmed Eldemery, Azza Elamir
No abstract text is available yet for this article.
May 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28444216/dietary-metabolites-derived-from-gut-microbiota-critical-modulators-of-epigenetic-changes-in-mammals
#17
Mohd Iqbal Bhat, Rajeev Kapila
The mammalian gastrointestinal tract harbors trillions of commensal microorganisms, collectively known as the microbiota. The microbiota is a critical source of environmental stimuli and, thus, has a tremendous impact on the health of the host. The microbes within the microbiota regulate homeostasis within the gut, and any alteration in their composition can lead to disorders that include inflammatory bowel disease, allergy, autoimmune disease, diabetes, mental disorders, and cancer. Hence, restoration of the gut flora following changes or imbalance is imperative for the host...
April 22, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28443466/promoter-methylation-and-gene-polymorphism-are-two-independent-events-in-regulation-of-gstp1-gene-expression
#18
Aaliya Bhat, A Masood, K A Wani, Younus Ahmad Bhat, Bushra Nissar, Nuzhat Shaheen Khan, B A Ganai
Breast carcinogenesis is a multistep process, involving both genetic and epigenetic modification process of genes, involved in diverse pathways ranging from DNA repair to metabolic processes. This study was undertaken to assess the role of promoter methylation of GSTP1 gene, a member of glutathione-S-transferase family of enzymes, in relation to its expression, polymorphism, and clinicopathological parameters. Tissue samples were taken from breast cancer patients and paired with their normal adjacent tissues...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28442587/combined-aurka-and-h3k9-methyltransferase-targeting-inhibits-cell-growth-by-inducing-mitotic-catastrophe
#19
Angela Mathison, Ann Salmonson, Mckenna Missfeldt, Jennifer Bintz, Monique Williams, Sarah Kossak, Asha Nair, Thiago M de Assuncao, Trace A Christensen, Navtej S Buttar, Juan L Iovanna, Robert Huebert, Gwen Lomberk
The current integrative pathobiological hypothesis states that pancreatic cancer (PDAC) develops and progresses in response to an interaction between known oncogenes and downstream epigenomic regulators. Congruently, this study tests a new combinatorial therapy based on the inhibition of the Aurora kinase A (AURKA) oncogene and one of its targets, the H3K9 methylation-based epigenetic pathway. This therapeutic combination is effective at inhibiting the in vitro growth of PDAC cells both, in monolayer culture systems, and in 3D spheroids and organoids...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28442585/next-gen-sequencing-analysis-and-algorithms-for-pdx-and-cdx-models
#20
Garima Khandelwal, Maria Romina Girotti, Christopher Smowton, Sam Taylor, Chris Wirth, Marek Dynowski, Kristopher K Frese, Ged Brady, Caroline Dive, Richard Marais, Crispin Miller
Patient-derived xenograft (PDX) and CTC-derived explant (CDX) models are powerful methods for the study of human disease. In cancer research, these methods have been applied to multiple questions including the study of metastatic progression, genetic evolution and therapeutic drug responses. Since PDX and CDX models can recapitulate the highly heterogeneous characteristics of a patient tumor, as well as their response to chemotherapy, there is considerable interest in combining them with next-generation sequencing (NGS) in order to monitor the genomic, transcriptional, and epigenetic changes that accompany oncogenesis...
April 25, 2017: Molecular Cancer Research: MCR
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