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https://www.readbyqxmd.com/read/28214899/therapeutic-targeting-of-epithelial-plasticity-programs-focus-on-the-epithelial-mesenchymal-transition
#1
Reem Malek, Hailun Wang, Kekoa Taparra, Phuoc T Tran
Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28213207/epimetabolites-discovering-metabolism-beyond-building-and-burning
#2
REVIEW
Megan R Showalter, Tomas Cajka, Oliver Fiehn
Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include regulation of histone demethylation in epigenetics, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, stem cell pluripotency status, inhibition of nitric oxide signaling and others. Such modified compounds, defined as epimetabolites, have functions distinct from classic hormones as well as removed from generic anabolism and catabolism...
February 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28212714/droplet-based-digital-pcr-application-in-cancer-research
#3
G Perkins, H Lu, F Garlan, V Taly
The efficient characterization of genetic and epigenetic alterations in oncology, virology, or prenatal diagnostics requires highly sensitive and specific high-throughput approaches. Nevertheless, with the use of conventional methods, sensitivity and specificity were largely limited. By partitioning individual target molecules within distinct compartments, digital PCR (dPCR) could overcome these limitations and detect very rare sequences with unprecedented precision and sensitivity. In dPCR, the sample is diluted such that each individual partition will contain no more than one target sequence...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28212444/sumo-modification-of-a-heterochromatin-histone-demethylase-jmjd2a-enables-viral-gene-transactivation-and-viral-replication
#4
Wan-Shan Yang, Mel Campbell, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification of chromatin has profound effects on transcription regulation. By using Kaposi's sarcoma associated herpesvirus (KSHV) as a model, we recently demonstrated that epigenetic modification of viral chromatin by SUMO-2/3 is involved in regulating gene expression and viral reactivation. However, how this modification orchestrates transcription reprogramming through targeting histone modifying enzymes remains largely unknown. Here we show that JMJD2A, the first identified Jumonji C domain-containing histone demethylase, is the histone demethylase responsible for SUMO-2/3 enrichment on the KSHV genome during viral reactivation...
February 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28212191/endothelial-cell-metabolism-an-update-anno-2017
#5
Laure-Anne Teuwen, Nihed Draoui, Charlotte Dubois, Peter Carmeliet
PURPOSE OF REVIEW: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. RECENT FINDINGS: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28211524/epigenetic-and-genetic-dissections-of-uv-induced-global-gene-dysregulation-in-skin-cells-through-multi-omics-analyses
#6
Yao Shen, Milda Stanislauskas, Gen Li, Deyou Zheng, Liang Liu
To elucidate the complex molecular mechanisms underlying the adverse effects UV radiation (UVR) on skin homeostasis, we performed multi-omics studies to characterize UV-induced genetic and epigenetic changes. Human keratinocytes from a single donor treated with or without UVR were analyzed by RNA-seq, exome-seq, and H3K27ac ChIP-seq at 4 h and 72 h following UVR. Compared to the relatively moderate mutagenic effects of UVR, acute UV exposure induced substantial epigenomic and transcriptomic alterations, illuminating a previously underappreciated role of epigenomic and transcriptomic instability in skin pathogenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210910/astrocyte-induced-reelin-expression-drives-proliferation-of-her2-breast-cancer-metastases
#7
Rahul Jandial, Cecilia Choy, Danielle M Levy, Mike Y Chen, Khairul I Ansari
Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival...
February 17, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28210884/energy-balance-and-obesity-what-are-the-main-drivers
#8
Isabelle Romieu, Laure Dossus, Simón Barquera, Hervé M Blottière, Paul W Franks, Marc Gunter, Nahla Hwalla, Stephen D Hursting, Michael Leitzmann, Barrie Margetts, Chizuru Nishida, Nancy Potischman, Jacob Seidell, Magdalena Stepien, Youfa Wang, Klaas Westerterp, Pattanee Winichagoon, Martin Wiseman, Walter C Willett
PURPOSE: The aim of this paper is to review the evidence of the association between energy balance and obesity. METHODS: In December 2015, the International Agency for Research on Cancer (IARC), Lyon, France convened a Working Group of international experts to review the evidence regarding energy balance and obesity, with a focus on Low and Middle Income Countries (LMIC). RESULTS: The global epidemic of obesity and the double burden, in LMICs, of malnutrition (coexistence of undernutrition and overnutrition) are both related to poor quality diet and unbalanced energy intake...
February 17, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28209170/lincrnafezf1-as1-represses-p21-expression-to-promote-gastric-cancer-proliferation-through-lsd1-mediated-h3k4me2-demethylation
#9
Yan-Wen Liu, Rui Xia, Kai Lu, Min Xie, Fen Yang, Ming Sun, Wei De, Cailian Wang, Guozhong Ji
BACKGROUND: Although the prognosis of gastric cancer patients have a favorable progression, there are some patients with unusual patterns of locoregional and systemic recurrence. Therefore, a better understanding of early molecular events of the disease is needed. Current evidences demonstrate that long noncoding RNAs (lncRNAs) may be an important class of functional regulators involved in human gastric cancers development. Our previous studies suggest that HOTAIR contributes to gastric cancer development, and the overexpression of HOTAIR predicts a poor prognosis...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28207785/dna-methylation-of-the-fthl17-5-upstream-region-regulates-differential-fthl17-expression-in-lung-cancer-cells-and-germline-stem-cells
#10
Nana Aoki, Kentaro Mochizuki, Yasuhisa Matsui
The Ferritin heavy polypeptide-like 17 (Fthl17) gene is a member of the cancer/testis antigen gene family, and is preferentially expressed in cancer cells and in testis. Although DNA methylation has been linked to the regulation of human FTHL17 gene expression, detailed epigenetic regulation of its expression has not been investigated. To address this, we assessed the epigenetic regulation of murine Fthl17 gene expression in cancer cells and germ cells. Fthl17 was more highly expressed in testis, a murine lung cancer cell line, KLN205, and in germline stem cells (GSCs) than in normal lung tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28205577/epigenetic-signatures-of-invasive-status-in-populations-of-marine-invertebrates
#11
Alba Ardura, Anastasija Zaiko, Paloma Morán, Serge Planes, Eva Garcia-Vazquez
Epigenetics, as a DNA signature that affects gene expression and enables rapid reaction of an organism to environmental changes, is likely involved in the process of biological invasions. DNA methylation is an epigenetic mechanism common to plants and animals for regulating gene expression. In this study we show, for the first time in any marine species, significant reduction of global methylation levels during the expansive phase of a pygmy mussel (Xenostrobus securis) recent invasion in Europe (two-year old), while in older introductions such epigenetic signature of invasion was progressively reduced...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203307/epigenetic-strategies-to-reverse-drug-resistance-in-heterogeneous-multiple-myeloma
#12
REVIEW
Mark E Issa, Farnaz Sedigheh Takhsha, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Wim Vanden Berghe, Muriel Cuendet
Multiple myeloma (MM) is a hematological malignancy, which remains incurable because most patients eventually relapse or become refractory to current treatments. Due to heterogeneity within the cancer cell microenvironment, cancer cell populations employ a dynamic survival strategy to chemotherapeutic treatments, which frequently results in a rapid acquisition of therapy resistance. Besides resistance-conferring genetic alterations within a tumor cell population selected during drug treatment, recent findings also reveal non-mutational mechanisms of drug resistance, involving a small population of "cancer stem cells" (CSCs) which are intrinsically more refractory to the effects of a variety of anticancer drugs...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28203090/exploring-targeted-therapy-of-osteosarcoma-using-proteomics-data
#13
Parunya Chaiyawat, Jongkolnee Settakorn, Apiruk Sangsin, Pimpisa Teeyakasem, Jeerawan Klangjorhor, Aungsumalee Soongkhaw, Dumnoensun Pruksakorn
Despite multimodal therapeutic treatments of osteosarcoma (OS), some patients develop resistance to currently available regimens and eventually end up with recurrent or metastatic outcomes. Many attempts have been made to discover effective drugs for improving outcome; however, due to the heterogeneity of the disease, new therapeutic options have not yet been identified. This study aims to explore potential targeted therapy related to protein profiles of OS. In this review of proteomics studies, we extracted data on differentially expressed proteins (DEPs) from archived literature in PubMed and our in-house repository...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28202042/hoxc8-regulates-self-renewal-differentiation-and-transformation-of-breast-cancer-stem-cells
#14
Mansi Shah, Ryan Cardenas, Belinda Wang, Jenny Persson, Nigel P Mongan, Anna Grabowska, Cinzia Allegrucci
BACKGROUND: Homeobox genes are master regulators of cell fate during embryonic development and their expression is altered in cancer. By regulating the balance between cell proliferation and differentiation, they maintain homeostasis of normal tissues. Here, we screened the expression of homeobox genes in mammary stem cells to establish their role in stem cells transformation in breast cancer. METHODS: Using a Homeobox Genes PCR array, we screened 83 homeobox genes in normal cancer breast stem/progenitor cells isolated by flow cytometry...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28199384/basic-studies-on-epigenetic-carcinogenesis-of-low-dose-exposure-to-1-trichloromethyl-1-2-3-4-tetrahydro-%C3%AE-carboline-taclo-in-vitro
#15
Renjie Wang, Yi Cui, Yi Xu, Joseph Irudayaraj
1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) has been widely studied as a neurotoxic substance, however, only few reports have explored its effect on carcinogenicity. Since the aberrant modification of DNA methylation occurs very early in almost all human cancers, the focus of this study is to assess the carcinogenicity of TaClo by characterizing alterations of the epigenetic state, specifically, DNA methylation, upon exposure to TaClo in a HEK 293 model cell line. Our results suggest that TaClo could induce global DNA hypomethylation and transcriptional repression of critical tumor suppressor genes by increasing their promoter methylation...
2017: PloS One
https://www.readbyqxmd.com/read/28199194/regulation-of-mitochondrial-gene-expression-the-epigenetic-enigma
#16
Archibold Mposhi, Monique Gp Van der Wijst, Klaas Nico Faber, Marianne G Rots
Epigenetics provides an important layer of information on top of the DNA sequence and is essential for establishing gene expression profiles. Extensive studies have shown that nuclear DNA methylation and histone modifications influence nuclear gene expression. However, it remains unclear whether mitochondrial DNA (mtDNA) undergoes similar epigenetic changes to regulate mitochondrial gene expression. Recently, it has been shown that mtDNA is differentially methylated in various diseases such as diabetes and colorectal cancer...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28199193/epigenetic-and-risk-factors-of-testicular-germ-cell-tumors-a-brief-review
#17
Daniel Adrian Landero-Huerta, Rosa Maria Vigueras-Villasenor, Emiy Yokoyama-Rebollar, Elena Arechaga-Ocampo, Julio Cesar Rojas-Castaneda, Francisco Jimenez-Trejo, Margarita Chavez-Saldana
Testicular germ cell cancer (TGCT) is the most common malignancy among young adult males, which has become important due to its increased incidence and mortality in the population worldwide. The etiology is multifactorial. Recent studies have shown some associations between the development of isolated TGCT and certain risk factors, such as exposure to endocrine disruptors, cryptorchidism, and family history of cancer, in order to identify the key pieces in carcinogenesis. Some of the most important findings in recent years is the association of different genes, such as c-KIT/KITLG, expression of the miR-371-373 cluster and protein expression as c-KIT and POU5F1 in the development of this neoplasia, and the identification of new molecular markers as TGFBR3 gene, identifying aberrant methylation patterns in promoter regions of several genes, expression of miR-1297 which regulates PTEN and protein expression as DMTR1...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28198667/pan-cancer-analysis-of-frequent-dna-co-methylation-patterns-reveals-consistent-epigenetic-landscape-changes-in-multiple-cancers
#18
Jie Zhang, Kun Huang
BACKGROUND: DNA methylation is the major form of epigenetic modifications through which the cell regulates the gene expression and silencing. There have been extensive studies on the roles of DNA methylation in cancers, and several cancer drugs were developed targeting this process. However, DNA co-methylation cluster has not been examined in depth, and co-methylation in multiple cancer types has never been studied previously. RESULTS: In this study, we applied newly developed lmQCM algorithm to mine co-methylation clusters using methylome data from 11 cancer types in TCGA database, and found frequent co-methylated gene clusters exist in these cancer types...
January 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28198450/identification-of-methylation-driven-differentially-expressed-stxbp6-as-a-novel-biomarker-in-lung-adenocarcinoma
#19
Govinda Lenka, Mong-Hsun Tsai, Hsin-Chieh Lin, Jen-Hao Hsiao, Yi-Ching Lee, Tzu-Pin Lu, Jang-Ming Lee, Chung-Ping Hsu, Liang-Chuan Lai, Eric Y Chuang
DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r ≤ -0...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196408/somatic-mutations-in-murine-models-of-leukemia-and-lymphoma-disease-specificity-and-clinical-relevance
#20
Liat Goldberg, Sheryl M Gough, Fan Lee, Christine Dang, Robert L Walker, Yeulin J Zhu, Sven Bilke, Marbin Pineda, Masahiro Onozawa, Yang Jo Chung, Paul S Meltzer, Peter D Aplan
Malignant transformation is a multistep process that is dictated by acquisition of multiple genomic aberrations that provide growth and survival advantage. During the post genomic era, high throughput genomic sequencing has advanced exponentially, leading to identification of countless cancer associated mutations with potential for targeted therapy. Mouse models of cancer serve as excellent tools to examine the functionality of gene mutations and their contribution to the malignant process. However, it remains unclear whether the genetic events that occur during transformation are similar in mice and humans...
February 14, 2017: Genes, Chromosomes & Cancer
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