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Angeline S Andrew, John A Baron, Lynn F Butterly, Arief A Suriawinata, Gregory J Tsongalis, Christina M Robinson, Christopher I Amos
Although serrated polyps were historically considered to pose little risk, it is now understood that progression down the serrated pathway could account for as many as 15%-35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P) is the most prevalent pre-invasive serrated lesion. Our objective was to identify the CpG loci that are persistently hyper-methylated during serrated carcinogenesis, from the early SSA/P lesion through the later cancer phases of neoplasia development. We queried the loci hyper-methylated in serrated cancers within our rightsided SSA/Ps from the New Hampshire Colonoscopy Registry, using the Illumina Infinium Human Methylation 450 k panel to comprehensively assess the DNA methylation status...
March 2, 2017: International Journal of Molecular Sciences
Milena Doroszko, Marcin Chrusciel, Kirstine Belling, Susanna Vuorenoja, Marlene Dalgaard, Henrik Leffers, H Bjørn Nielsen, Ilpo Huhtaniemi, Jorma Toppari, Nafis A Rahman
Specific inbred strains and transgenic inhibin-α Simian Virus 40 T antigen (inhα/Tag) mice are genetically susceptible to gonadectomy-induced adrenocortical neoplasias. We identified altered gene expression in prepubertally gonadectomized (GDX) inhα/Tag and wild-type (WT) mice. Besides earlier reported Gata4 and Lhcgr, we found up-regulated Esr1, Prlr-rs1, and down-regulated Grb10, Mmp24, Sgcd, Rerg, Gnas, Nfatc2, Gnrhr, Igf2 in inhα/Tag adrenal tumors. Sex-steroidogenic enzyme genes expression (Srd5a1, Cyp19a1) was up-regulated in tumors, but adrenal-specific steroidogenic enzyme (Cyp21a1, Cyp11b1, Cyp11b2) down-regulated...
January 25, 2017: Molecular and Cellular Endocrinology
Jar-Yi Ho, Ren-Jun Hsu, Jui-Ming Liu, Szu-Chi Chen, Guo-Shiou Liao, Hong-Wei Gao, Cheng-Ping Yu
Aberrant activation of the Ras/ERK pathway mediates breast cancer initiation and aggressiveness. Therefore, it is important to identify miRNAs that modulate the Ras/ERK pathway during breast carcinogenesis and progression. The Ras GTPase superfamily member RERG (Ras-related and estrogen-regulated growth inhibitor) acts as a tumor suppressor to reduce breast cancer cell proliferation and tumor formation and has been suggested to have a regulatory role in the Ras/ERK pathway. In this study, we found that RERG exerted its tumor suppressor role by attenuating the activation of Ras/ERK signaling effectors...
April 4, 2017: Oncotarget
Mohammad A Aleskandarany, Rezvan Abduljabbar, Ibraheem Ashankyty, Ahmed Elmouna, Dena Jerjees, Simak Ali, Laki Buluwela, Maria Diez-Rodriguez, Carlos Caldas, Andrew R Green, Ian O Ellis, Emad A Rakha
Differential prognostic roles of Androgen Receptor (AR) have been proposed in breast cancer (BC) depending on tumour oestrogen receptor (ER) status. This study aimed to evaluate the prognostic and/or predictive significance of AR expression in invasive BC. In this study AR expression was studied on a large (n = 1141) consecutive series of early-stage (I-III) BC using tissue microarray and immunohistochemistry (IHC). AR mRNA expression was assessed in a subset of cases. The prognostic impact of AR mRNA expression was externally validated using the online BC gene expression data sets (n = 25 data sets, 4078 patients)...
September 2016: Breast Cancer Research and Treatment
Xiang Luo, Rong Huang, Hongru Sun, Yupeng Liu, Haoran Bi, Jing Li, Hongyuan Yu, Jiamei Sun, Shangqun Lin, Binbin Cui, Yashuang Zhao
The relationship between the DNA methylation status of the CpG islands of multiple genes in blood leukocytes in CRC susceptibility and prognosis, as well as possible interactions with dietary factors on CRC risk are unclear. We carried out a case-control study including 421 CRC patients and 506 controls to examine the associations between six genes (AOX-1, RARB2, RERG, ADAMTS9, IRF4, and FOXE-1), multiple CpG site methylation (MCSM) and susceptibility to CRC. High-level MCSM (MCSM-H) was defined as methylation of greater than or equal to 2 of 5 candidate genes (except for RARB2); low-level MCSM (MCSM-L) was when 1 candidate gene was methylated; non-MCSM was when none of the candidate genes were methylated...
2016: Scientific Reports
M X Sui, H H Wang, Z W Wang
The current study aimed to investigate the coding sequence, polymorphisms, and expression of the RERG gene in indigenous Chinese goats. cDNA of RERG, obtained through reverse transcription PCR was analyzed using bioinformatic techniques. Polymorphisms in the exon regions of the RERG gene were identified and their associations with growth traits in three varieties of indigenous Chinese goats were investigated. Expression of the RERG gene in three goat breeds of the same age was detected using real-time quantitative PCR...
2015: Genetics and Molecular Research: GMR
Ji Eun Kim, So Hae Park, Moon Hwa Kwak, Jun Go, Eun Kyoung Koh, Sung Hwa Song, Ji Eun Sung, Hee Seob Lee, Jin Tae Hong, Dae Youn Hwang
To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number...
2015: PloS One
Aguirre A de Cubas, Esther Korpershoek, Lucia Inglada-Pérez, Eric Letouzé, Maria Currás-Freixes, Agustin F Fernández, Iñaki Comino-Méndez, Francesca Schiavi, Veronika Mancikova, Graeme Eisenhofer, Massimo Mannelli, Guiseppe Opocher, Henri Timmers, Felix Beuschlein, Ronald de Krijger, Alberto Cascon, Cristina Rodríguez-Antona, Mario F Fraga, Judith Favier, Anne-Paule Gimenez-Roqueplo, Mercedes Robledo
PURPOSE: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors, associated with highly variable postoperative evolution. The scarcity of reliable PPGL prognostic markers continues to complicate patient management. In this study, we explored genome-wide DNA methylation patterns in the context of PPGL malignancy to identify novel prognostic markers. EXPERIMENTAL DESIGN: We retrospectively investigated DNA methylation patterns in PPGL with and without metastases using high-throughput DNA methylation profiling data (Illumina 27K) from two large, well-characterized discovery (n = 123; 24 metastatic) and primary validation (n = 154; 24 metastatic) series...
July 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
D Monsivais, M T Dyson, P Yin, J S Coon, A Navarro, G Feng, S S Malpani, M Ono, C M Ercan, J J Wei, M E Pavone, E Su, S E Bulun
In endometriosis, stromal and epithelial cells from the endometrium form extrauterine lesions and persist in response to estrogen (E2) and prostaglandin E2 (PGE2). Stromal cells produce excessive quantities of estrogen and PGE2 in a feed-forward manner. However, it is unknown how estrogen stimulates cell proliferation and survival for the establishment and persistence of disease. Previous studies suggest that estrogen receptor-β (ERβ) is strikingly overexpressed in endometriotic stromal cells. Thus, we integrated genome-wide ERβ binding data from previously published studies in breast cells and gene expression profiles in human endometriosis and endometrial tissues (total sample number = 81) and identified Ras-like, estrogen-regulated, growth inhibitor (RERG) as an ERβ target...
August 2014: Molecular Endocrinology
Desmond G Powe, Gopal Krishna R Dhondalay, Christophe Lemetre, Tony Allen, Hany O Habashy, Ian O Ellis, Robert Rees, Graham R Ball
BACKGROUND: Oestrogen receptor (ER) positive (luminal) tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus...
2014: PloS One
B Giessrigl, W M Schmidt, M Kalipciyan, M Jeitler, M Bilban, M Gollinger, S Krieger, W Jäger, R M Mader, G Krupitza
BACKGROUND: Breast cancer is the leading cause of cancer death in women living in the western hemisphere. Despite major advances in first-line endocrine therapy of advanced oestrogen receptor (ER)-positive breast cancer, the frequent recurrence of resistant cancer cells represents a serious obstacle to successful treatment. Understanding the mechanisms leading to acquired resistance, therefore, could pave the way to the development of second-line therapeutics. To this end, we generated an ER-positive breast cancer cell line (MCF-7) with resistance to the therapeutic anti-oestrogen fulvestrant (FUL) and studied the molecular changes involved in resistance...
November 12, 2013: British Journal of Cancer
Rongxi Yang, Bowang Chen, Katrin Pfütze, Stephan Buch, Verena Steinke, Elke Holinski-Feder, Sarah Stöcker, Witigo von Schönfels, Thomas Becker, Hans K Schackert, Brigitte Royer-Pokora, Matthias Kloor, Wolff H Schmiegel, Reinhard Büttner, Christoph Engel, Jesus Lascorz Puertolas, Asta Försti, Nelli Kunkel, Peter Bugert, Stefan Schreiber, Michael Krawczak, Clemens Schafmayer, Peter Propping, Jochen Hampe, Kari Hemminki, Barbara Burwinkel
Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a large number of genetic risk factors involved in CRC have not been understood. Copy number variations (CNVs) might partly contribute to the 'missing heritability' of CRC. An increased overall burden of CNV has been identified in several complex diseases, whereas the association between the overall CNV burden and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the Affymetrix 6...
February 2014: Carcinogenesis
Jong J Kim, Jan Němec, Rita Papp, Robert Strongin, Jonathan J Abramson, Guy Salama
Bradycardia prolongs action potential (AP) durations (APD adaptation), enhances dispersion of repolarization (DOR), and promotes tachyarrhythmias. Yet, the mechanisms responsible for enhanced DOR and tachyarrhythmias remain largely unexplored. Ca(2+) transients and APs were measured optically from Langendorff rabbit hearts at high (150 × 150 μm(2)) or low (1.5 × 1.5 cm(2)) magnification while pacing at a physiological (120 beats/min) or a slow heart rate (SHR = 50 beats/min). Western blots and pharmacological interventions were used to elucidate the regional effects of bradycardia...
March 15, 2013: American Journal of Physiology. Heart and Circulatory Physiology
Suee Lee, Hyuk-Chan Kwon, Sung-Hyun Kim, Sung Yong Oh, Ji Hyun Lee, Yeon-Su Lee, Daekwan Seo, Jin-Yeong Han, Hyo-Jin Kim
BACKGROUND: Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD). METHODS: Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls...
September 2012: Korean Journal of Hematology
Luis Carretero, Francisco Barros, Pablo Miranda, Jorge Fernández-Trillo, Angeles Machín, Pilar de la Peña, Pedro Domínguez
While the thyrotropin-releasing hormone (TRH) effect of raising intracellular Ca(2+) levels has been shown to rely on G(q/11) and PLC activation, the molecular mechanisms involved in the regulation of ERG K(+) channels by TRH are still partially unknown. We have analysed the effects of βγ scavengers, Akt/PKB inactivation, and TRH receptor (TRH-R) overexpression on such regulation in native and heterologous expression cell systems. In native rat pituitary GH(3) cells β-ARK/CT, Gα(t), and phosducin significantly reduced TRH inhibition of rERG currents, whereas in HEK-H36/T1 cells permanently expressing TRH-R and hERG, neither of the βγ scavengers affected the TRH-induced shift in V (1/2)...
April 2012: Pflügers Archiv: European Journal of Physiology
Christoph Birner, Oliver Husser, Andreas Jeron, Munhie Rihm, Sabine Fredersdorf, Markus Resch, Peter Schmid, Dierk Endemann, Günter Riegger, Andreas Luchner
Heart failure causes electrophysiological changes in the heart. Downregulation of repolarizing K+-currents leads to a prolongation of the cardiac action potential. Nevertheless, little is known about the differential expression of atrial and ventricular K+-channels in the failing heart. Ten rabbits underwent progressive rapid right ventricular pacing for 30 days. Digitized ECGs and echocardiograms were obtained. Left ventricular and left atrial tissue was harvested and mRNA levels of BNP, Kv4.3, rERG, Kv1...
May 2012: Naunyn-Schmiedeberg's Archives of Pharmacology
Daniel Alan Kerr, James L Wittliff
Primary breast carcinomas expressing both estrogen and progesterone receptors are most likely to respond to tamoxifen therapy, especially in patients with early-stage lesions. However, certain patients exhibit clinicopathologic features suggesting good prognosis relapse within 10 years, justifying a search for biomarkers identifying patients at risk for recurrence. Nine candidate genes associated with estrogen signaling were selected from microarray studies and combined with those for conventional biomarkers (ESR1, PGR, ERBB2)...
October 2011: Hormones & Cancer
Bodil Oster, Kasper Thorsen, Philippe Lamy, Tomasz K Wojdacz, Lise Lotte Hansen, Karin Birkenkamp-Demtröder, Karina D Sørensen, Søren Laurberg, Torben F Orntoft, Claus L Andersen
In our study, whole-genome methylation arrays were applied to identify novel genes with tumor specific DNA methylation of promoter CpG islands in pre-malignant and malignant colorectal lesions. Using a combination of Illumina HumanMethylation27 beadchips, Methylation-Sensitive High Resolution Melting (MS-HRM) analysis, and Exon arrays (Affymetrix) the DNA methylation pattern of ∼14,000 genes and their transcript levels were investigated in six normal mucosas, six adenomas and 30 MSI and MSS carcinomas. Sixty eight genes with tumor-specific hypermethylation were identified (p < 0...
December 15, 2011: International Journal of Cancer. Journal International du Cancer
T Chile, M L Corrêa-Giannella, M A H Z Fortes, M D Bronstein, M B Cunha-Neto, D Giannella-Neto, R R Giorgi
BACKGROUND: Pituitary tumors account for approximately 10-15% of intracranial neoplasms. AIM: Using the cDNA microarray method, we have previously compared expression under two distinct conditions: a pool of 4 clinically non-functioning pituitary adenomas (NFPA) and a spinal cord metastasis of a non-functioning pituitary carcinoma, in order to gain biological insights into genomic changes of pituitary neoplasias. In the present study, we further investigated the mRNA expression of 3 selected genes previously described as being involved in other neoplasias based on a series of 60 pituitary adenomas: CRABP1 (cellular retinoic acid binding protein 1), GRP (gastrin-releasing peptide), and RERG (Ras-related, estrogen- regulated, growth inhibitor)...
September 2011: Journal of Endocrinological Investigation
Ch A Izmaĭlov, M M Zimachev
The frog retina was stimulated with light flashes homogeneous in space but not time. The time heterogeneity of stimulation was created by abrupt change of a referent stimulus for a stimulus with different luminance. Such changes form a time pattern, as well as sharp borders of luminance between the neighbor areas of the visual field form a spatial pattern. The electroretinogram recorded in response to presentation of a triad of stimuli: the onset of a short flash of homogeneous light after long dark (or light) adaptation of a retina, brief sequence of the referent and test light flashes varied in luminance, and the offset, with returning to the initial level of adaptation...
September 2010: Zhurnal Vyssheĭ Nervnoĭ Deiatelnosti Imeni I P Pavlova
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