Articles

Epigenetic abnormalities in myeloproliferative neoplasms: a target for novel therapeutic strategies

The myeloproliferative neoplasms (MPNs) are a group of clonal hematological malignancies characterized by a hypercellular bone marrow and a tendency to develop thrombotic complications and to evolve to myelofi...

Authors: John Mascarenhas, Nitin Roper, Pratima Chaurasia and Ronald Hoffman

Role of DNA methylation in head and neck cancer

Head and neck cancer (HNC) is a heterogenous and complex entity including diverse anatomical sites and a variety of tumor types displaying unique characteristics and different etilogies. Both environmental and...

Authors: Semra Demokan and Nejat Dalay

MicroRNA-mediated drug resistance in breast cancer

Chemoresistance is one of the major hurdles to overcome for the successful treatment of breast cancer. At present, there are several mechanisms proposed to explain drug resistance to chemotherapeutic agents, i...

Authors: Kristy R. Kutanzi, Olga V. Yurchenko, Frederick A. Beland, Vasyl’ F. Checkhun and Igor P. Pogribny

H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues

A sequence variant of histone H2A called H2AX is one of the key components of chromatin involved in DNA damage response induced by different genotoxic stresses. Phosphorylated H2AX (γH2AX) is rapidly concentra...

Authors: Denis V. Firsanov, Liudmila V. Solovjeva and Maria P. Svetlova

Evolutional and clinical implications of the epigenetic regulation of protein glycosylation

Protein N glycosylation is an ancient posttranslational modification that enriches protein structure and function. The addition of one or more complex oligosaccharides (glycans) to the backbones of the majorit...

Authors: Tomislav Horvat, Vlatka Zoldoš and Gordan Lauc

Insufficient DNA methylation affects healthy aging and promotes age-related health problems

DNA methylation plays an integral role in development and aging through epigenetic regulation of genome function. DNA methyltransferase 1 (Dnmt1) is the most prevalent DNA methyltransferase that maintains geno...

Authors: Liang Liu, Thomas van Groen, Inga Kadish, Yuanyuan Li, Deli Wang, Smitha R. James, Adam R. Karpf and Trygve O. Tollefsbol

Transcriptional modulation by VIP: a rational target against inflammatory disease

Vasoactive intestinal peptide (VIP) is a pleiotropic, highly conserved, peptide found in many different biological systems throughout invertebrate phyla. VIP is produced by cells of the immune system but also ...

Authors: Hiba Ibrahim, Paul Barrow and Neil Foster

ABT-737 and/or folate reverse the PDGF-induced alterations in the mitochondrial apoptotic pathway in low-grade glioma patients

Elevated activation of the platelet-derived growth factor (PDGF) pathway, apoptosis evasion phenotype, and global DNA hypomethylation are hallmarks frequently observed in cancers, such as in low-grade glioma (...

Authors: Emilie Debien, Eric Hervouet, Fabien Gautier, Philippe Juin, Francois M. Vallette and Pierre-Francois Cartron

Epigenetic management of major psychosis

Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pa...

Authors: Jacob Peedicayil

Epigenetic regulation of mucin genes in human cancers

Mucins are high molecular weight glycoproteins that play important roles in diagnostic and prognostic prediction and in carcinogenesis and tumor invasion. Regulation of expression of mucin genes has been studi...

Authors: Norishige Yamada, Sho Kitamoto, Seiya Yokoyama, Tomofumi Hamada, Masamichi Goto, Hideaki Tsutsumida, Michiyo Higashi and Suguru Yonezawa

The role of epigenetic dysregulation in the epidemic of allergic disease

The epidemic of allergic disease in early life is one of the clearest indicators that the developing immune system is vulnerable to modern environmental changes. A range of environmental exposures epidemiologi...

Authors: Susan Prescott and Richard Saffery

Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications

Epigenetic changes in long interspersed nuclear element-1s (LINE-1s or L1s) occur early during the process of carcinogenesis. A lower methylation level (hypomethylation) of LINE-1 is common in most cancers, an...

Authors: Nakarin Kitkumthorn and Apiwat Mutirangura

Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-azacytidine and valproic acid

5-azacytidine (AZA) has become standard treatment for patients with higher-risk myelodysplastic syndrome (MDS). Response rate is about 50% and response duration is limited. Histone deactylase (HDAC) inhibitors...

Authors: Andrea Kuendgen, Gesine Bug, Oliver G. Ottmann, Detlef Haase, Julie Schanz, Barbara Hildebrandt, Kathrin Nachtkamp, Judith Neukirchen, Ariane Dienst, Rainer Haas, Ulrich Germing and Norbert Gattermann

Can metabolic plasticity be a cause for cancer? Warburg–Waddington legacy revisited

Fermentation of glucose to lactate in the presence of sufficient oxygen, known as aerobic glycolysis or Warburg effect, is a universal phenotype of cancer cells. Understanding its origin and role in cellular i...

Authors: Paike Jayadeva Bhat, Lalit Darunte, Venkatesh Kareenhalli, Jaswandi Dandekar and Abhay Kumar

Identification of ChIP-seq mapped targets of HP1β due to bombesin/GRP receptor activation

Epithelial cells lining the adult colon do not normally express gastrin-releasing peptide (GRP) or its receptor (GRPR). In contrast, GRP/GRPR can be aberrantly expressed in human colorectal cancer (CRC) includ...

Authors: Robert Tell, Q. Tian Wang, Adam Blunier and Richard V. Benya

Epigenetic mechanisms in virus-induced tumorigenesis

About 15–20% of human cancers worldwide have viral etiology. Emerging data clearly indicate that several human DNA and RNA viruses, such as human papillomavirus, Epstein–Barr virus, Kaposi’s sarcoma-associated...

Authors: Elzbieta Poreba, Justyna Karolina Broniarczyk and Anna Gozdzicka-Jozefiak

The biological basis and clinical significance of hormonal imprinting, an epigenetic process

The biological phenomenon, hormonal imprinting, was named and defined by us (Biol Rev, 1980, 55, 47-63) 30 years ago, after many experimental works and observations. Later, similar phenomena were also named to...

Authors: György Csaba

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condi...

Authors: Steven G. Gray

The elements of human cyclin D1 promoter and regulation involved

Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites suc...

Authors: Zhi-yi Guo, Xiao-hui Hao, Fei-Fei Tan, Xin Pei, Li-Mei Shang, Xue-lian Jiang and Fang Yang

Impact of vitamin D metabolism on clinical epigenetics

The bioactive vitamin D (VD) metabolite, 1,25-dihydroxyvitamin D₃ regulates essential pathways of cellular metabolism and differentiation via its nuclear receptor (VDR). Molecular mechanisms which are known to pl...

Authors: Heidrun Karlic and Franz Varga

The transposon-driven evolutionary origin and basis of histone deacetylase functions and limitations in disease prevention

Histone deacetylases (HDACs) are homologous to prokaryotic enzymes that removed acetyl groups from non-histone proteins before the evolution of eukaryotic histones. Enzymes inherited from prokaryotes or from a...

Authors: Gregory W. Peek and Trygve O. Tollefsbol

5-Aza-2′-deoxycytidine stress response and apoptosis in prostate cancer

While studying on epigenetic regulatory mechanisms (DNA methylation at C-5 of –CpG– cytosine and demethylation of methylated DNA) of certain genes (FAS, CLU, E-cadh, CD44, and Cav-1) associated with prostate c...

Authors: Aditi Patra, Moonmoon Deb, Rajvir Dahiya and Samir Kumar Patra

Interaction of SET domains with histones and nucleic acid structures in active chromatin

Changes in the normal program of gene expression are the basis for a number of human diseases. Epigenetic control of gene expression is programmed by chromatin modifications—the inheritable “histone code”—the ...

Authors: Wladyslaw A. Krajewski and Oleg L. Vassiliev

Epigenetic mechanisms and genome stability

Epigenetic marks are well recognized as heritable chemical modifications of DNA and chromatin that induce chromatin structural changes thereby affecting gene activity. A lesser-known phenomenon is the pervasiv...

Authors: Emily L. Putiri and Keith D. Robertson

Molecular marks for epigenetic identification of developmental and cancer stem cells

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and e...

Authors: Samir Kumar Patra, Moonmoon Deb and Aditi Patra

The possibility of evidence-based psychiatry: depression as a case

Considering psychiatry as a medical discipline, a diagnosis identifying a disorder should lead to an effective therapy. Such presumed causality is the basis of evidence-based psychiatry. We examined the streng...

Authors: Drozdstoy Stojanov, Jakob Korf, Peter de Jonge and Georgi Popov

Association between hMLH1 hypermethylation and JC virus (JCV) infection in human colorectal cancer (CRC)

Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorec...

Authors: Alex Vilkin and Yaron Niv

Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy

Heritable changes in gene expression that are not based upon alterations in the DNA sequence are defined as epigenetics. The most common mechanisms of epigenetic regulation are the methylation of CpG islands w...

Authors: Julia M. Wagner, Björn Hackanson, Michael Lübbert and Manfred Jung

Epigenetic targets of bioactive dietary components for cancer prevention and therapy

The emergent interest in cancer epigenetics stems from the fact that epigenetic modifications are implicated in virtually every step of tumorigenesis. More interestingly, epigenetic changes are reversible heri...

Authors: Syed M. Meeran, Amiya Ahmed and Trygve O. Tollefsbol

Cancer: evolutionary, genetic and epigenetic aspects

There exist two paradigms about the nature of cancer. According to the generally accepted one, cancer is a by-product of design limitations of a multi-cellular organism (Greaves, Nat Rev Cancer 7:213–221, 2007...

Authors: Anatoly V. Lichtenstein

Introductory editorial

Authors: Ulrich Mahlknecht and Jean-Pierre Issa

The sirtuins in the pathogenesis of cancer

Aging is the natural trace that time leaves behind on life during blossom and maturation, culminating in senescence and death. This process is accompanied by a decline in the healthy function of multiple organ...

Authors: Susanne Voelter-Mahlknecht and Ulrich Mahlknecht

Histone deacetylase inhibitors: clinical implications for hematological malignancies

Histone modifications have widely been implicated in cancer development and progression and are potentially reversible by drug treatments. The N-terminal tails of each histone extend outward through the DNA st...

Authors: Francesco Paolo Tambaro, Carmela Dell’Aversana, Vincenzo Carafa, Angela Nebbioso, Branka Radic, Felicetto Ferrara and Lucia Altucci

Targeting the epigenome: effects of epigenetic treatment strategies on genomic stability in healthy human cells

Epigenetic treatment concepts have long been ascribed as being tumour-selective. Over the last decade, it has become evident that epigenetic mechanisms are essential for a wide range of intracellular functions...

Authors: Jan C. Purrucker and Ulrich Mahlknecht

DNA hypermethylation markers of poor outcome in laryngeal cancer

This study examined molecular (DNA hypermethylation), clinical, histopathological, demographical, smoking, and alcohol variables to assess diagnosis (early versus late stage) and prognosis (survival) outcomes ...

Authors: Josena K. Stephen, Kang Mei Chen, Veena Shah, Shaleta Havard, Alissa Kapke, Mei Lu, Michael S. Benninger and Maria J. Worsham

Continuous multiparametric monitoring of cell metabolism in response to transient overexpression of the sirtuin deacetylase SIRT3

The analysis and visualisation of research data in an environment which is most similar to living conditions belong to the most challenging claims of present scientific research endeavours. To date, the effect...

Authors: Christian-Lars Dransfeld, Hamed Alborzinia, Stefan Wölfl and Ulrich Mahlknecht

Histone deacetylases in viral infections

Chromatin remodeling and gene expression are regulated by histone deacetylases (HDACs) that condense the chromatin structure by deacetylating histones. HDACs comprise a group of enzymes that are responsible fo...

Authors: Georges Herbein and Daniel Wendling

Histone deacetylase inhibitors: a new and promising drug class for the treatment of arthritis?

Authors: Éric Toussirot, Kashif Aziz Khan and Georges Herbein

Challenge and promise: the role of miRNA for pathogenesis and progression of malignant melanoma

microRNAs are endogenous noncoding RNAs that are implicated in gene regulation. More recently, miRNAs have been shown to play a pivotal role in multiple cellular processes that interfere with tumorigenesis. He...

Authors: Salma Essa, N. Denzer, U. Mahlknecht, R. Klein, E. M. Collnot and J. Reichrath