Breaking News
September 20, 2018 - Could Household Cleaners Make Your Kid Fat?
September 20, 2018 - Addiction nonprofit makes searching for services simple
September 20, 2018 - We are bombarded by thousands of diverse species and chemicals | News Center
September 20, 2018 - Experts to Present Prostate Cancer Advances at Patient Summit
September 20, 2018 - Alector announces initiation of Phase 1 trial of AL001 for treating frontotemporal dementia
September 20, 2018 - Pfizer’s 20vPnC vaccine receives Breakthrough Therapy designation from FDA
September 20, 2018 - Study could allow doctors to screen patients at risk from Aspergillus
September 20, 2018 - Emergex signs MoU with Brazil’s Fiocruz for development of viral vaccines
September 20, 2018 - The ‘real you’ is a myth – we constantly create false memories to achieve the identity we want
September 20, 2018 - Researchers describe cell mechanism that optimizes proteins production in stressful situations
September 20, 2018 - Cell Medica successfully doses first patient with CMD-501 targeting pediatric neuroblastoma
September 20, 2018 - Senators unveil legislation to protect patients against surprise medical bills
September 20, 2018 - Study provides insights into development of special-purpose cosmetic products
September 20, 2018 - Research shows enlarged genotype-phenotype correlation for three-base pair deletion in NF1
September 20, 2018 - DePuy Synthes introduces CONCORDE LIFT Expandable Interbody Device at EUROSPINE 2018
September 20, 2018 - Manx Telecom unveils MT clearSound that improves clarity of mobile phone calls
September 20, 2018 - Mediterranean-style diet appears to reduce stroke risk in women
September 20, 2018 - AbbVie Announces Patient-Reported Outcomes Data from Three Pivotal Phase 3 Studies of Risankizumab, Showing Significant Improvements in Health-Related Quality of Life for Patients with Psoriasis
September 20, 2018 - Characterization of pregnancy microbiome reveals variations in bacterial diversity
September 20, 2018 - New guidance for treatment of bone loss in hematologic stem cell transplant Recipients
September 20, 2018 - Experts to present research on prevention, management of dysphagia at international conference
September 20, 2018 - New study focuses on two-way gene switches controlling gene activity
September 20, 2018 - Zika virus could become a weapon against brain cancer
September 20, 2018 - Home-based video game exercises can reduce chronic low back pain in older people, study finds
September 20, 2018 - Investigators find that bile acids reduce cocaine reward
September 20, 2018 - Cannabinoid drugs reduce perceived unpleasantness of painful stimuli and increase tolerance
September 20, 2018 - Health care companies’ data could enable more accurate flu season forecasts
September 20, 2018 - Geroscience takes center stage in Journal of the American Medical Association
September 20, 2018 - Ambient Particulate Matter Linked to Emergency Asthma Care
September 20, 2018 - Patient satisfaction with plastic surgery—it’s the surgeon, not the practice
September 20, 2018 - Medicine is a team sport – and that’s exactly how it should be
September 20, 2018 - Logos Biosystems releases new electrophoretic tissue clearing system with twice the features in half the space
September 20, 2018 - Novel micro-platform reveals never-before-seen behaviors of cancer cells
September 20, 2018 - PAREXEL partners with Datavant to enhance clinical study design and generate real-world evidence
September 20, 2018 - Robert Koch Institute publishes new data on allergies, mental health problems, and accident injuries
September 20, 2018 - Study finds higher readmission rates in for-profit hospitals
September 20, 2018 - Encouraging youth to do strength-based exercises could help tackle child obesity
September 20, 2018 - Sleep apnea, congenital heart disease in hospitalized infants strongly associated with death
September 20, 2018 - Researchers find way to map mysterious content of non-coding RNA
September 20, 2018 - Air Pollutants Reach Placenta, Might Harm Fetus: Study
September 20, 2018 - Sleep apnea, congenital heart disease may be deadly mix for hospitalized infants
September 20, 2018 - My relative has cancer, should I worry? Encouraging cascade genetic testing
September 20, 2018 - Investigators determine specific treatable traits that can predict future asthma attacks
September 20, 2018 - More doctor visits can lower risk of suicide attempts in fibromyalgia patients
September 20, 2018 - Computer avatars play role in diagnosis of dementia
September 20, 2018 - Addition of CTLA4 targeted therapy to PD-1 targeted therapy may benefit patients with ovarian cancer
September 20, 2018 - ASPREE trial explores whether low dose aspirin can prolong good health in elderly people
September 20, 2018 - ATS publishes new guideline focused on weight loss strategies for sleep apnea patients
September 20, 2018 - The Current issue of “The view from here” is concerned with Drug Delivery
September 19, 2018 - Sleep apnea could favour tumor growth at young ages
September 19, 2018 - Stealth vaping fad hidden from parents, teachers
September 19, 2018 - Witnessing school violence linked to later risk of psycho-social and academic impairment
September 19, 2018 - Common household cleaners could make children overweight by changing gut microbiota
September 19, 2018 - Salk research in yeast leads to serendipitous finding about hypomyelinating leukodystrophy
September 19, 2018 - Study: Overweight or obese women may have increased risk of urinary incontinence
September 19, 2018 - Study shows how cellular waste disposal processes also promote inflammation
September 19, 2018 - New multidisciplinary microsurgery microscope, PROVIDO, introduced by Leica
September 19, 2018 - Phase 2b STORM Data Evaluating Selinexor in Patients with Penta-Refractory Multiple Myeloma Presented at the Society of Hematologic Oncology 2018 Annual Meeting
September 19, 2018 - Decisions recruiting gut feelings seen as reflection of true self, more assuredly held, study says
September 19, 2018 - How AI can improve end-of-life care
September 19, 2018 - UNIST and Ulsan initiate research collaboration to develop human organs-on-chips
September 19, 2018 - Study highlights key role of migrating shoals of fish in sustaining deep-ocean microorganisms
September 19, 2018 - Disagreeable individuals can benefit most from behaving more compassionately, finds study
September 19, 2018 - Janssen Submits New Drug Application to U.S. FDA Seeking Approval of Erdafitinib for the Treatment of Metastatic Urothelial Cancer
September 19, 2018 - Neuroplasticity is increased but dysregulated in the aging brain, study finds
September 19, 2018 - Suicide: A public health crisis
September 19, 2018 - Infants using popular anti-reflux medicines are not at increased risk of lung infections
September 19, 2018 - Stanford team will participate in NIH-funded study of tobacco policies | News Center
September 19, 2018 - Women with high levels of anti-Müllerian hormone more likely to develop breast cancer
September 19, 2018 - Researchers use larval zebrafish model to reveal role of locus coeruleus in anesthesia
September 19, 2018 - Effects of prematurity found to be more severe for the brains of males than females
September 19, 2018 - NIH funds CWRU to investigate new imaging approach for diagnosing peripheral arterial disease
September 19, 2018 - NUS researchers develop new device for quick and accurate screening of diseases
September 19, 2018 - Leading nutritionist explains about different types of iron in oral supplements
September 19, 2018 - New Crest Gum & Enamel Repair toothpaste may boost enamel repair and reverse gingivitis
September 19, 2018 - Analysis does not find any safety concerns of bivalent HPV vaccine
September 19, 2018 - Many Older Adults Transition to Long-Term Benzodiazepine Use
September 19, 2018 - Caregiving – resources – older adults: MedlinePlus Medical Encyclopedia
September 19, 2018 - Research shows that cystic fibrosis impacts growth in the womb
September 19, 2018 - Study shows how head, neck positioning affects concussion risk | News Center
Researchers target abnormal epigenetic mechanisms involved in childhood cancers

Researchers target abnormal epigenetic mechanisms involved in childhood cancers

image_pdfDownload PDFimage_print

Several childhood cancer cell types show features of immature neural cells, and there is evidence suggesting that these tumors may arise from neural crest stem cells that underwent abnormal changes during embryonic development. One such cancer is Ewing sarcoma. Although combinatorial treatment protocols encompassing chemotherapy, surgery, and radiotherapy have improved outcomes, many patients still suffer from a poor prognosis.

Typically, the pathogenesis of Ewing sarcoma includes fusion of the EWS and FLI-1 genes. The resulting EWSR1-FLI-1 protein induces aberrant epigenomic reprogramming, which alters acetylation and methylation, leading to chromatin remodeling. Chromatin is a structurally condensed form of DNA, and its condensation state regulates gene expression patterns epigenetically. Highly condensed chromatin can suppress the expression of genes that control differentiation, thereby keeping cancer cells in a poorly differentiated, stem cell-like state that facilitates tumor progression.

A team of researchers at the Cancer and Neurobiology Laboratory and the Pediatric Oncology Service at the Federal University of Rio Grande do Sul (UFRGS) and its university hospital (Hospital de Clínicas de Porto Alegre, HCPA), and the Children’s Cancer Institute (Instituto do Câncer Infantil, ICI), in Porto Alegre, Brazil, in collaboration with Dr. Carol J. Thiele, Deputy Chief of the Pediatric Oncology Branch at the National Cancer Institute, National Institutes of Health (NIH), in Bethesda, MD, USA, have targeted proteins that regulate the chromatin state of DNA in Ewing sarcoma cells with the goal of hindering malignant tumor growth. In a new study published in the journal Molecular Neurobiology (preprint available at http://www.biorxiv.org), lead author Dr. Barbara Kunzler Souza and colleagues were able to induce chromatic relaxation in Ewing sarcoma cells by treating them with a compound that inhibits histone deacetylases. The treatment reduced expression of the EWSR1-FLI-1 oncogene as well as expression of other genes associated with pluripotency and cell viability, while impairing the cells’ ability to survive and proliferate. Decreased survival of stem-like cancer cells and re-expression of a neuronal differentiation marker were also observed.

In a previous study by the same group, Dr. Viviane Rösner de Almeida and colleagues demonstrated that treating human neuroblastoma cells with epigenetic agents that inhibit either histone deacetylases or DNA methyltransferase potentiated the ability of a retinoid-based therapy to impair cell proliferation and reduced the expression of oncogene products, including c-Myc and Bmi1. Neuroblastoma–the most common extracranial solid childhood cancer accounting for ~15% of pediatric cancer deaths–is another pediatric cancer thought to originate from a developmental malfunction of embryonic neural crest cells. Dr. Rafael Roesler, associate professor of pharmacology at UFRGS and senior author of the studies, has said that “targeting epigenetic processes that regulate chromatin state, such as histone acetylation and DNA methylation, seems to be an effective experimental approach to inducing desirable biological changes in cells from childhood tumors that may arise from defects in embryonic development.”

Dr. André T. Brunetto, Research Diretor at ICI, added, “It is our hope that uncovering molecular mechanisms involved in childhood cancer progression will result in translational opportunities that can be explored in clinical studies.” Dr. Caroline Brunetto de Farias, ICI Head of Cellular and Molecular Research, says the findings from cell culture experiments are helping the team identify clinically useful drugs that target epigenetic mechanisms and have the potential to be investigated as putative adjuvant therapies in animal and human studies.

Tagged with:

About author

Related Articles