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epigenetics in oncology

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https://www.readbyqxmd.com/read/29305580/the-epigenetically-regulated-mir-494-associates-with-stem-cell-phenotype-and-induces-sorafenib-resistance-in-hepatocellular-carcinoma
#1
Daniela Pollutri, Clarissa Patrizi, Sara Marinelli, Catia Giovannini, Elena Trombetta, Ferdinando A Giannone, Maurizio Baldassarre, Santina Quarta, Y P Vandewynckel, A Vandierendonck, H Van Vlierberghe, Laura Porretti, Massimo Negrini, Luigi Bolondi, Laura Gramantieri, Francesca Fornari
Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, especially in patients not amenable for curative treatments. The multi-kinase inhibitor sorafenib represents the first-line treatment option for advanced HCC; nevertheless, its effectiveness is limited due to tumor heterogeneity as well as innate or acquired drug resistance, raising the need for new therapeutic strategies. MicroRNAs (miRNAs) involvement in treatment response as well as their safety and efficacy in preclinical models and clinical trials have been widely documented in the oncologic field, including HCC...
January 5, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29233295/novel-approaches-to-targeting-brd4
#2
REVIEW
Olesya A Kharenko, Henrik C Hansen
Inhibition of bromo and extra-terminal (BET) bromodomains, including BRD4, has emerged as a new exciting epigenetic target for oncology, in particular. Recently, novel alternatives to the traditional use of reversible small molecules have emerged, including proteolytic targeting BET agents and irreversible binding inhibitors. These alternatives to reversible inhibitors may offer some advantage and can be used as tools to further decipher the underlying biology. Supportive pre-clinical data have these novel approaches bound for clinical development in the near future...
June 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/29230998/-research-progress-on-the-detection-method-of-dna-methylation-and-its-application-in-forensic-science
#3
REVIEW
Y C Nie, L J Yu, H Guan, Y Zhao, H B Rong, B W Jiang, T Zhang
As an important part of epigenetic marker, DNA methylation involves in the gene regulation and attracts a wide spread attention in biological auxology, geratology and oncology fields. In forensic science, because of the relative stable, heritable, abundant, and age-related characteristics, DNA methylation is considered to be a useful complement to the classic genetic markers for age-prediction, tissue-identification, and monozygotic twins' discrimination. Various methods for DNA methylation detection have been validated based on methylation sensitive restriction endonuclease, bisulfite modification and methylation-CpG binding protein...
June 2017: Fa Yi Xue za Zhi
https://www.readbyqxmd.com/read/29215703/design-synthesis-and-characterization-of-%C3%AE-%C3%AE-unsaturated-carboxylic-acid-and-its-urea-based-derivatives-that-explores-novel-epigenetic-modulators-in-human-non-small-cell-lung-cancer-a549-cell-line
#4
Anusha Chidambaram, S H Kavya, Ramesh Kumar Chidambaram, Rajasekaran Subbiah, John Marshal Jayaraj, Karthikeyan Muthusamy, Ravikumar Vilwanathan
Histone deacetylase inhibitors (HDACi) are a small molecule chemotherapeutics that target the chromatin remodeling through the regulation of histone and non-histone proteins. These inhibitors directed against HDAC enzymes have become an important therapeutic tool in oncology; consequently, scientific efforts have fortified the quest for newer and novel HDACi, which forces the design of structurally innovative HDACi. Various urea containing compounds exhibited admirable anticancer activity. On the basis of these observations, we design and synthesize HDAC specific blocker molecules which are specifically besieged towards class I, class II and class IV HDAC isoforms to enhance the structural assortment for HDACi...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29174566/the-roles-of-pathology-in-targeted-therapy-of-women-with-gynecologic-cancers
#5
Rajmohan Murali, Rachel N Grisham, Robert A Soslow
The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor...
November 23, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29168653/utilizing-biomarkers-in-colorectal-cancer-an-interview-with-ajay-goel
#6
Ajay Goel
Ajay Goel, PhD, is a Professor and Director, Center for Gastrointestinal Research, and Director, Center for Translational Genomics and Oncology, at the Baylor Scott & White Research Institute, Baylor University Medical Center in Dallas, Texas. Dr Goel has spent more than 20 years researching cancer and has been the lead author or contributor to over 240 scientific articles published in peer-reviewed international journals and several book chapters. He is also a primary inventor on more than 15 international patents aimed at developing various biomarkers for the diagnosis, prognosis and prediction of gastrointestinal cancers...
November 23, 2017: Future Oncology
https://www.readbyqxmd.com/read/29093018/the-future-of-surveillance-in-the-context-of-cancer-predisposition-through-the-murky-looking-glass
#7
EDITORIAL
David Malkin, Kim E Nichols, Joshua D Schiffman, Sharon E Plon, Garrett M Brodeur
At least 10% of children with cancer harbor a disease-associated pathogenic variant in a known cancer predisposition gene. It is widely accepted that pathogenic variants affecting other genes, epigenetic factors, or abnormalities in additional gene products may contribute to the etiology of many more childhood cancers. Effective preventive measures exist for only a few cancer types associated with predisposing conditions, but the development and implementation of surveillance protocols aimed at reducing morbidity and mortality in at-risk children through the early detection of cancer has emerged as an important clinical tool...
November 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29058986/identification-of-clinical-and-biologic-correlates-associated-with-outcome-in-children-with-adrenocortical-tumors-without-germline-tp53-mutations-a-st-jude-adrenocortical-tumor-registry-and-children-s-oncology-group-study
#8
Emilia Modolo Pinto, Carlos Rodriguez-Galindo, Stanley B Pounds, Lei Wang, Michael R Clay, Geoffrey Neale, Elizabeth A R Garfinkle, Catherine G Lam, Carolyn Fein Levy, Alberto S Pappo, Gerard P Zambetti, Raul C Ribeiro
Purpose The clinical features, pathogenesis, and outcomes in children with adrenocortical tumors (ACTs) without germline TP53 mutations have not been systematically studied. Herein, we describe these correlates and analyze their association with outcome. Patients and Methods Genomic DNA was analyzed for TP53, CTNNB1, CDKN1C, ATRX, and chromosome 11p15 abnormalities. β-catenin expression and Ki-67 labeling index (LI) were evaluated by immunostaining. Primary end points were progression-free (PFS) and overall survival...
December 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29057232/expanded-molecular-interrogation-for-potential-actionable-targets-in-non-squamous-non-small-cell-lung-cancer
#9
REVIEW
Kah Weng Lau, Claudia Seng, Tony K H Lim, Daniel S W Tan
The advent of targeted therapies has established new standards of care for defined molecular subsets of non-small cell lung cancer (NSCLC). Not only has this led to significant changes in the routine clinical management of lung cancer e.g., multiplexed genomic testing, but it has provided important principles and benchmarks for determining "actionability". At present, the clinical paradigms are most evolved for EGFR mutations and ALK rearrangements, where multiple randomized phase III trials have determined optimal treatment strategies in both treatment naïve and resistant settings...
September 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29029592/pharmacoepigenetics-and-toxicoepigenetics-novel-mechanistic-insights-and-therapeutic-opportunities
#10
Volker M Lauschke, Isabel Barragan, Magnus Ingelman-Sundberg
Pharmacological treatment and exposure to xenobiotics can cause substantial changes in epigenetic signatures. The majority of these epigenetic changes, caused by the compounds in question, occur downstream of transcriptional activation mechanisms, whereby the epigenetic alterations can create a transcriptional memory and stably modulate cell function. The increasing understanding of epigenetic mechanisms and their importance in disease has prompted the development of therapeutic interventions that target epigenetic modulatory mechanisms, particularly in oncology where inhibitors of epigenetic-modifying proteins (epidrugs) have been successfully used in treatment, mostly in combination with standard-of-care chemotherapy, provoking either direct cytotoxicity or inhibiting resistance to anticancer drugs...
October 13, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/29028415/crispr-cas9-mediated-noncoding-rna-editing-in-human-cancers
#11
Jie Yang, Xiaodan Meng, Jinchang Pan, Nan Jiang, Chengwei Zhou, Zhenhua Wu, Zhaohui Gong
Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system...
October 13, 2017: RNA Biology
https://www.readbyqxmd.com/read/29016348/parp-1-and-parp-2-activity-in-cancer-induced-cachexia-potential-therapeutic-implications
#12
Esther Barreiro, Joaquim Gea
Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28994387/-the-identity-of-normal-and-cancer-stem-cells
#13
Lucie Laplane, Éric Solary
What is a stem cell? Is stemness an intrinsic or extrinsic property? What role does the microenvironment play in the stemness identity? We distinguish four identities for normal and cancerous stem cells and explore their consequences for therapeutic strategy choice in the oncology setting. Acquisition of genetic and epigenetic alterations during cell transformation and disease progression questions the stability of the stemness property's identity in cancers.
October 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28992739/pharmacogenetic-and-pharmacogenomic-considerations-of-asthma-treatment
#14
REVIEW
Maria Gabriella Matera, Barbara Rinaldi, Luigino Calzetta, Mario Cazzola
Pharmacogenetic and pharmacogenomic approaches are already utilized in some areas, such as oncology and cardiovascular disease, for selecting appropriate patients and/or establishing treatment and dosing guidelines. This is not true in asthma although many patients have different responses to drug treatment due to genetic factors. Areas covered: Several genetic factors that affect the pharmacotherapeutic responses to asthma medications, such as β2-AR agonists, corticosteroids, and leukotriene modifiers and could contribute to significant between-person variability in response are described...
November 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28978058/mir-30e-is-overexpressed-in-prostate-cancer-and-promotes-nf-%C3%AE%C2%BAb-mediated-proliferation-and-tumor-growth
#15
Shawn M Egan, Ellen Karasik, Leigh Ellis, Sandra O Gollnick
According to the CDC prostate cancer (CaP) has the highest incidence and second highest mortality rate amongst cancers in American men. Constitutive NF-κB activation is a hallmark of CaP and this pathway drives many pro-tumorigenic characteristics of CaP cells, including cell proliferation and survival. An activated NF-κB gene signature is predictive of CaP progression and biochemical recurrence following therapeutic intervention. However, the mechanisms that perpetuate NF-κB activation are incompletely understood...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978016/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#16
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28948003/the-hedgehog-gli-pathway-in-embryonic-development-and-cancer-implications-for-pulmonary-oncology-therapy
#17
REVIEW
Leonel Armas-López, Joaquín Zúñiga, Oscar Arrieta, Federico Ávila-Moreno
Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies. Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935018/-progress-of-epigenetic-methylation-in-lung-cancer-research
#18
Shaowei Zhang, Zhiqiang Xue
Lung cancer is becoming an increasing threat to Chinese residents and its incidence continues to rise while the treatment effect is far from satisfactory. Hence, it is essential to improve the level of early diagnosis, treatment, prognosis in lung cancer. An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence. The epigenetic studies, such as DNA methylation and histone methylation, are progressing rapidly in oncology research. A comprehensive understanding of its development status and existing problems is of great significance for the future research and the implementation of precision medicine...
September 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28931097/-approaching-new-pharmacotherapy-options-in-pain-treatment
#19
András Telekes
The evolution of medicine is noticeable in most therapeutic areas, the worse the current therapeutic result, the more quick the improvement. This is especially true in such areas that require substantial social resources, namely oncology, diabetology and CNS diseases. Pain is not a disease, it is a symptom. Pain is one of the most important components of human suffering thus it deserves special attention. In recent years new formulations of old medicines were introduced rather than new medicines. Maybe ziconitide is the last pain killer with new mechanism of action which was approved by FDA in 2004...
September 20, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28930219/qigong-in-cancer-care-theory-evidence-base-and-practice
#20
Penelope Klein
Background: The purpose of this discussion is to explore the theory, evidence base, and practice of Qigong for individuals with cancer. Questions addressed are: What is qigong? How does it work? What evidence exists supporting its practice in integrative oncology? What barriers to wide-spread programming access exist? Methods: Sources for this discussion include a review of scholarly texts, the Internet, PubMed, field observations, and expert opinion. Results: Qigong is a gentle, mind/body exercise integral within Chinese medicine...
January 12, 2017: Medicines (Basel, Switzerland)
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