2017 CM08 Mcken 0801 Post.Pdf
Total Page：16
File Type：pdf, Size：1020Kb
Load more
Recommended publications
-
ERG Dependence Distinguishes Developmental Control of Hematopoietic Stem Cell Maintenance from Hematopoietic Specification
Downloaded from genesdev.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification Samir Taoudi,1,2,6 Thomas Bee,3 Adrienne Hilton,1 Kathy Knezevic,3 Julie Scott,4 Tracy A. Willson,1,2 Caitlin Collin,1 Tim Thomas,1,2 Anne K. Voss,1,2 Benjamin T. Kile,1,2 Warren S. Alexander,2,5 John E. Pimanda,3 and Douglas J. Hilton1,2 1Molecular Medicine Division, The Walter and Eliza Institute of Medical Research, Melbourne, Parkville, Victoria 3052, Australia; 2Department of Medical Biology, The University of Melbourne, Melbourne, Parkville, Victoria 3010, Australia; 3Lowy Cancer Research Centre, The Prince of Wales Clinical School, University of New South Wales, Sydney 2052, Australia; 4Microinjection Services, The Walter and Eliza Institute of Medical Research, Melbourne, Parkville, Victoria 3052, Australia; 5Cancer and Haematology Division, The Walter and Eliza Institute of Medical Research, Melbourne, Parkville, Victoria 3052, Australia Although many genes are known to be critical for early hematopoiesis in the embryo, it remains unclear whether distinct regulatory pathways exist to control hematopoietic specification versus hematopoietic stem cell (HSC) emergence and function. Due to their interaction with key regulators of hematopoietic commitment, particular interest has focused on the role of the ETS family of transcription factors; of these, ERG is predicted to play an important role in the initiation of hematopoiesis, yet we do not know if or when ERG is required. Using in vitro and in vivo models of hematopoiesis and HSC development, we provide strong evidence that ERG is at the center of a distinct regulatory program that is not required for hematopoietic specification or differentiation but is critical for HSC maintenance during embryonic development. -
Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development
International Journal of Molecular Sciences Review Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development Charles Ducker * and Peter E. Shaw * Queen’s Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK * Correspondence: [email protected] (C.D.); [email protected] (P.E.S.) Abstract: Genome expansion, whole genome and gene duplication events during metazoan evolution produced an extensive family of ETS genes whose members express transcription factors with a conserved winged helix-turn-helix DNA-binding domain. Unravelling their biological roles has proved challenging with functional redundancy manifest in overlapping expression patterns, a common consensus DNA-binding motif and responsiveness to mitogen-activated protein kinase signalling. Key determinants of the cellular repertoire of ETS proteins are their stability and turnover, controlled largely by the actions of selective E3 ubiquitin ligases and deubiquitinases. Here we discuss the known relationships between ETS proteins and enzymes that determine their ubiquitin status, their integration with other developmental signal transduction pathways and how suppression of ETS protein ubiquitination contributes to the malignant cell phenotype in multiple cancers. Keywords: E3 ligase complex; deubiquitinase; gene fusions; mitogens; phosphorylation; DNA damage 1. Introduction Citation: Ducker, C.; Shaw, P.E. Cell growth, proliferation and differentiation are complex, concerted processes that Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer rely on careful regulation of gene expression. Control over gene expression is maintained and Development. Int. J. Mol. Sci. through signalling pathways that respond to external cellular stimuli, such as growth 2021, 22, 5119. https://doi.org/ factors, cytokines and chemokines, that invoke expression profiles commensurate with 10.3390/ijms22105119 diverse cellular outcomes. -
Genitourinary Pathology (Including Renal Tumors)
LABORATORY INVESTIGATION THE BASIC AND TRANSLATIONAL PATHOLOGY RESEARCH JOURNAL LI VOLUME 99 | SUPPLEMENT 1 | MARCH 2019 2019 ABSTRACTS GENITOURINARY PATHOLOGY (INCLUDING RENAL TUMORS) (776-992) MARCH 16-21, 2019 PLATF OR M & 2 01 9 ABSTRACTS P OSTER PRESENTATI ONS EDUCATI ON C O M MITTEE Jason L. Hornick , C h air Ja mes R. Cook R h o n d a K. Y a nti s s, Chair, Abstract Revie w Board S ar a h M. Dr y and Assign ment Co m mittee Willi a m C. F a q ui n Laura W. La mps , Chair, C ME Subco m mittee C ar ol F. F ar v er St e v e n D. Billi n g s , Interactive Microscopy Subco m mittee Y uri F e d ori w Shree G. Shar ma , Infor matics Subco m mittee Meera R. Ha meed R aj a R. S e et h al a , Short Course Coordinator Mi c h ell e S. Hir s c h Il a n W ei nr e b , Subco m mittee for Unique Live Course Offerings Laksh mi Priya Kunju D a vi d B. K a mi n s k y ( Ex- Of ici o) A n n a M ari e M ulli g a n Aleodor ( Doru) Andea Ri s h P ai Zubair Baloch Vi nita Parkas h Olca Bast urk A nil P ar w a ni Gregory R. Bean , Pat h ol o gist-i n- Trai ni n g D e e p a P atil D a ni el J. -
Inducible Transgene Expression in PDX Models
Liu et al. Biomarker Research (2020) 8:46 https://doi.org/10.1186/s40364-020-00226-z RESEARCH Open Access Inducible transgene expression in PDX models in vivo identifies KLF4 as a therapeutic target for B-ALL Wen-Hsin Liu1, Paulina Mrozek-Gorska2, Anna-Katharina Wirth1, Tobias Herold1,3, Larissa Schwarzkopf1, Dagmar Pich2, Kerstin Völse1, M. Camila Melo-Narváez2, Michela Carlet1, Wolfgang Hammerschmidt2,4 and Irmela Jeremias1,5,6* Abstract Background: Clinically relevant methods are not available that prioritize and validate potential therapeutic targets for individual tumors, from the vast amount of tumor descriptive expression data. Methods: We established inducible transgene expression in clinically relevant patient-derived xenograft (PDX) models in vivo to fill this gap. Results: With this technique at hand, we analyzed the role of the transcription factor Krüppel-like factor 4 (KLF4) in B-cell acute lymphoblastic leukemia (B-ALL) PDX models at different disease stages. In competitive preclinical in vivo trials, we found that re-expression of wild type KLF4 reduced the leukemia load in PDX models of B-ALL, with the strongest effects being observed after conventional chemotherapy in minimal residual disease (MRD). A nonfunctional KLF4 mutant had no effect on this model. The re-expression of KLF4 sensitized tumor cells in the PDX model towards systemic chemotherapy in vivo. It is of major translational relevance that azacitidine upregulated KLF4 levels in the PDX model and a KLF4 knockout reduced azacitidine-induced cell death, suggesting that azacitidine can regulate KLF4 re-expression. These results support the application of azacitidine in patients with B-ALL as a therapeutic option to regulate KLF4. -
Ten Commandments for a Good Scientist
Unravelling the mechanism of differential biological responses induced by food-borne xeno- and phyto-estrogenic compounds Ana María Sotoca Covaleda Wageningen 2010 Thesis committee Thesis supervisors Prof. dr. ir. Ivonne M.C.M. Rietjens Professor of Toxicology Wageningen University Prof. dr. Albertinka J. Murk Personal chair at the sub-department of Toxicology Wageningen University Thesis co-supervisor Dr. ir. Jacques J.M. Vervoort Associate professor at the Laboratory of Biochemistry Wageningen University Other members Prof. dr. Michael R. Muller, Wageningen University Prof. dr. ir. Huub F.J. Savelkoul, Wageningen University Prof. dr. Everardus J. van Zoelen, Radboud University Nijmegen Dr. ir. Toine F.H. Bovee, RIKILT, Wageningen This research was conducted under the auspices of the Graduate School VLAG Unravelling the mechanism of differential biological responses induced by food-borne xeno- and phyto-estrogenic compounds Ana María Sotoca Covaleda Thesis submitted in fulfillment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. dr. M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Tuesday 14 September 2010 at 4 p.m. in the Aula Unravelling the mechanism of differential biological responses induced by food-borne xeno- and phyto-estrogenic compounds. Ana María Sotoca Covaleda Thesis Wageningen University, Wageningen, The Netherlands, 2010, With references, and with summary in Dutch. ISBN: 978-90-8585-707-5 “Caminante no hay camino, se hace camino al andar. Al andar se hace camino, y al volver la vista atrás se ve la senda que nunca se ha de volver a pisar” - Antonio Machado – A mi madre. -
Poster: Publikace 2008
Publikované Práce lékařů Šiklova Patologicko – anatomického ústavu a bioPtické laboratoře s.r.o. za rok 2008 Časopisy s „impact“ faktorem syringofibroadenoma associated with well-differentiated squamous cell 28. Kuroda N., Katto K., Yamaguchi T., Kawada T., ImamuraY., Hes O., Michal M., 42. Vazmitel M., Spagnolo D.V., Němcová J., Michal M., Kazakov D.V.: 1. Alvarado-Cabrero I., Perez-Montiel D.M., Hes, O.: Multicystic urothelial carcinoma. Am J Dermatopathol, 30, 572-574, 2008. Shuin T., Lee G.H.: Chromophobe renal cell carcinoma: Diagnostic ancillary Hidradenoma papilliferum with a ductal carcinoma in situ component. Case report and review of the literature. Am J Dermatopathol, 30, 392-394, 2008. carcinoma of the bladder with gland-like lumina and with signet-ring cells. 17. Kacerovska D., Michal M., Kreuzberg B., Mukensnabl P., Kazakov DV.: application of imprint cytology and fluorescencein situ hybridization of Acral calcified vascular leiomyoma of the skin: a rare clinicopathological chromosomes 10 and 21 in two cases of typical and eosinophilic variants. 43. Vazmitel M., Michal M., Kazakov D.V.: Merkel cell carcinoma with a A case report. Diagn Pathol, 3, 36, 2008. follicular lymphocytic infiltrate: report of two cases. Am J Dermatopathol, 2. Beneš Z., Chlumská A., Antoš Z., Kohout P., Sequens R.: Detection of variant of cutaneous vascular leiomyomas: report of 3 cases. J Amer Acad Med Mol Morphol, 41, 227-232, 2008. 29. Kuroda N., Kato K., Tamura M., Shiotsu T., Hes O., Michal M., Hagashima 30, 389-391, 2008. carcinoma by means of endoscopic cytoscopy in the area of ulcerative colitis. Dermatology, 59,1000-1004, 2008. -
RUNX1 Together with a Compendium of Hematopoietic Regulators, Chromatin Modifiers and Basal Transcr
Leukemia (2014) 28, 770–778 OPEN & 2014 Macmillan Publishers Limited All rights reserved 0887-6924/14 www.nature.com/leu ORIGINAL ARTICLE CBFB–MYH11/RUNX1 together with a compendium of hematopoietic regulators, chromatin modifiers and basal transcription factors occupies self-renewal genes in inv(16) acute myeloid leukemia A Mandoli1, AA Singh1, PWTC Jansen2, ATJ Wierenga3,4, H Riahi1, G Franci5, K Prange1, S Saeed1, E Vellenga3, M Vermeulen2, HG Stunnenberg1 and JHA Martens1 Different mechanisms for CBFb–MYH11 function in acute myeloid leukemia with inv(16) have been proposed such as tethering of RUNX1 outside the nucleus, interference with transcription factor complex assembly and recruitment of histone deacetylases, all resulting in transcriptional repression of RUNX1 target genes. Here, through genome-wide CBFb–MYH11-binding site analysis and quantitative interaction proteomics, we found that CBFb–MYH11 localizes to RUNX1 occupied promoters, where it interacts with TAL1, FLI1 and TBP-associated factors (TAFs) in the context of the hematopoietic transcription factors ERG, GATA2 and PU.1/SPI1 and the coregulators EP300 and HDAC1. Transcriptional analysis revealed that upon fusion protein knockdown, a small subset of the CBFb–MYH11 target genes show increased expression, confirming a role in transcriptional repression. However, the majority of CBFb–MYH11 target genes, including genes implicated in hematopoietic stem cell self-renewal such as ID1, LMO1 and JAG1, are actively transcribed and repressed upon fusion protein knockdown. Together these results suggest an essential role for CBFb–MYH11 in regulating the expression of genes involved in maintaining a stem cell phenotype. Leukemia (2014) 28, 770–778; doi:10.1038/leu.2013.257 Keywords: CBFb–MYH11; RUNX1; histone acetylation; acute myeloid leukemia; inv(16) INTRODUCTION Heterozygous Cbfb-Myh11 knock-in mice are embryonic lethal, Core-binding transcription factors (CBFs) have roles in stem cell with definitive hematopoiesis blocked at the stem-cell level. -
The Histone Methyltransferase MMSET/WHSC1 Activates TWIST1 to Promote an Epithelial–Mesenchymal Transition and Invasive Properties of Prostate Cancer
Oncogene (2013) 32, 2882–2890 & 2013 Macmillan Publishers Limited All rights reserved 0950-9232/13 www.nature.com/onc ORIGINAL ARTICLE The histone methyltransferase MMSET/WHSC1 activates TWIST1 to promote an epithelial–mesenchymal transition and invasive properties of prostate cancer T Ezponda1, R Popovic1, MY Shah1, E Martinez-Garcia1, Y Zheng2, D-J Min1, C Will1, A Neri3, NL Kelleher1,2,JYu1 and JD Licht1 Epigenetic deregulation of gene expression has a role in the initiation and progression of prostate cancer (PCa). The histone methyltransferase MMSET/WHSC1 (Multiple Myeloma SET domain) is overexpressed in a number of metastatic tumors, but its mechanism of action has not been defined. In this work, we found that PCa cell lines expressed significantly higher levels of MMSET compared with immortalized, non-transformed prostate cells. Knockdown experiments showed that, in metastatic PCa cell lines, dimethylation of lysine 36 and trimethylation of lysine 27 on histone H3 (H3K36me2 and H3K27me3, respectively) depended on MMSET expression, whereas depletion of MMSET in benign prostatic cells did not affect chromatin modifications. Knockdown of MMSET in DU145 and PC-3 tumor cells decreased cell proliferation, colony formation in soft agar and strikingly diminished cell migration and invasion. Conversely, overexpression of MMSET in immortalized, non-transformed RWPE-1 cells promoted cell migration and invasion, accompanied by an epithelial–mesenchymal transition (EMT). Among a panel of EMT-promoting genes analyzed, TWIST1 expression was strongly activated in response to MMSET. Chromatin immunoprecipitation analysis demonstrated that MMSET binds to the TWIST1 locus and leads to an increase in H3K36me2, suggesting a direct role of MMSET in the regulation of this gene. -
Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours
Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours Hellquist, Henrik; Paiva-Correia, António; Vander Poorten, Vincent; Quer, Miquel; Hernandez- Prera, Juan C; Andreasen, Simon; Zbären, Peter; Skalova, Alena; Rinaldo, Alessandra; Ferlito, Alfio Published in: Advances in Therapy DOI: 10.1007/s12325-019-01007-3 Publication date: 2019 Document version Publisher's PDF, also known as Version of record Document license: CC BY-NC Citation for published version (APA): Hellquist, H., Paiva-Correia, A., Vander Poorten, V., Quer, M., Hernandez-Prera, J. C., Andreasen, S., Zbären, P., Skalova, A., Rinaldo, A., & Ferlito, A. (2019). Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours. Advances in Therapy, 36(8), 1950-1974. https://doi.org/10.1007/s12325-019-01007-3 Download date: 01. okt.. 2021 Adv Ther (2019) 36:1950–1974 https://doi.org/10.1007/s12325-019-01007-3 ORIGINAL RESEARCH Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours Henrik Hellquist . Anto´nio Paiva-Correia . Vincent Vander Poorten . Miquel Quer . Juan C. Hernandez-Prera . Simon Andreasen . Peter Zba¨ren . Alena Skalova . Alessandra Rinaldo . Alfio Ferlito Received: May 2, 2019 / Published online: June 17, 2019 Ó The Author(s) 2019 ABSTRACT to investigate whether an accurate histological diagnosis of the 11 different types of benign Introduction: A vast increase in knowledge of epithelial salivary gland tumours is correlated to numerous aspects of malignant salivary gland any differences in their clinical behaviour. tumours has emerged during the last decade Methods: A search was performed for histolog- and, for several reasons, this has not been the ical classifications, recurrence rates and risks for case in benign epithelial salivary gland malignant transformation, treatment modali- tumours. -
GATA3-Controlled Nucleosome Eviction Drives MYC Enhancer Activity in T-Cell Development and Leukemia
Published OnlineFirst September 13, 2019; DOI: 10.1158/2159-8290.CD-19-0471 RESEARCH ARTICLE GATA3-Controlled Nucleosome Eviction Drives MYC Enhancer Activity in T-cell Development and Leukemia Laura Belver1, Alexander Y. Yang1, Robert Albero1, Daniel Herranz2,3, Francesco G. Brundu4, S. Aidan Quinn1, Pablo Pérez-Durán1, Silvia Álvarez1, Francesca Gianni1, Marissa Rashkovan1, Devya Gurung1, Pedro P. Rocha5, Ramya Raviram6,7, Clara Reglero1, Jose R. Cortés1, Anisha J. Cooke1, Agnieszka A. Wendorff1, Valentina Cordó8, Jules P. Meijerink8, Raúl Rabadan4,9, and Adolfo A. Ferrando1,4,10,11 ABSTRACT Long-range enhancers govern the temporal and spatial control of gene express ion; however, the mechanisms that regulate enhancer activity during normal and malig- nant development remain poorly understood. Here, we demonstrate a role for aberrant chromatin acces- sibility in the regulation of MYC expression in T-cell lymphoblastic leukemia (T-ALL). Central to this process, the NOTCH1-MYC enhancer (N-Me), a long-range T cell–specificMYC enhancer, shows dynamic changes in chromatin accessibility during T-cell specification and maturation and an aberrant high degree of chromatin accessibility in mouse and human T-ALL cells. Mechanistically, we demonstrate that GATA3- driven nucleosome eviction dynamically modulates N-Me enhancer activity and is strictly required for NOTCH1-induced T-ALL initiation and maintenance. These results directly implicate aberrant regulation of chromatin accessibility at oncogenic enhancers as a mechanism of leukemic transformation. SIGNIFICANCE: MYC is a major effector of NOTCH1 oncogenic programs in T-ALL. Here, we show a major role for GATA3-mediated enhancer nucleosome eviction as a driver of MYC expression and leuke- mic transformation. -
A034047-100 Top Secrets.Qxd 5/18/06 2:32 PM Page 1
A034047-100 Top Secrets.qxd 5/18/06 2:32 PM Page 1 TOP 100 SECRETS These secrets are 100 of the top board alerts. They summarize the concepts, principles, and most salient details of CT body scans. 1. Computed tomography (CT) differs from conventional radiography by forming a cross-sectional image, eliminating the superimposition of structures that occurs in plain film imaging because of compression of three-dimensional body structures onto the two-dimensional recording system. 2. The sensitivity of CT to subtle differences in x-ray attenuation is at least a factor of 10 higher than normally achieved by film screen recording systems because of the virtual elimination of scatter. 3. Radiation doses in CT range from 15–50 mGy, depending on exam type. In general, these doses are at least 10 times higher than in radiographic exams. 4. Always seek to optimize scan parameters to minimize patient dose consistent with diagnostic image quality: Minimize mAs, minimize kVp, maximize pitch, maximize slice thickness, and maximize collimator setting. 5. When scanning children, be sure to use pediatric protocols, not adult protocols. In pediatric protocols the CT scan parameters should be reduced so that radiation doses are optimized according to patient size. 6. Pregnant women should be scanned only if there is adequate justification to avoid unnecessary fetal irradiation. 7. Many of the side effects of contrast media are entirely or mainly due to high osmolality. The other causes of side effects due to contrast media are chemotoxicity (allergic-like symptoms), ion toxicity (interference with cellular function), and those caused by a high dose. -
The Erg Gene: a Human Gene Related to the Ets Oncogene (Cloning/Sequencing/Expression/Oncogene Homology) E
Proc. Nati. Acad. Sci. USA Vol. 84, pp. 6131-6135, September 1987 Biochemistry The erg gene: A human gene related to the ets oncogene (cloning/sequencing/expression/oncogene homology) E. SHYAM P. REDDY*t, VEENA N. RAOI, AND TAKIS S. PAPAS: tLaboratory of Molecular Oncology and *Programme Resources, Inc., National Cancer Institute, Frederick, MD 21701 Communicated by Max Tishler, May 26, 1987 ABSTRACT We have isolated a cDNA clone representing the complete coding sequence of a human gene named erg, RP C P R P R C R related to the ets oncogene. Nucleotide sequence analysis of this X7 ,i cDNA (4.6 kilobases long) revealed that this gene encodes a (erg 1) ATG TAA AATAAA 363-residue protein whose predicted amino acid sequence showed a homology of -40% and -7O% to two domains corresponding to the 5' and 3' regions of v-ets oncogene, 200 bp respectively. A 3.2- to 3.6-kilobase and -5-kilobase transcript FIG. 1. Analysis of the coding region of the -5-kb human ergl of the erg gene, which differ in size from those ofthe previously mRNA performed on a single phage "4.6-kb cDNA spanning the described Hu-ets 1 and Hu-ets 2 genes, were observed in entire region. Hatched boxes represent 5' (left) and 3' (right) different cells. These results suggest that the erg gene is a homologous regions of v-ets oncogene. Initiation codon (ATG), member of the ets oncogene family. termination codon (TAA), and polyadenylylation signal (AATAAA) are also shown. Horizontal arrow represents an 8-bp sequence, a avian which is repeated twice as a direct repeat in another cDNA clone E26 is replication-defective acute leukemia virus, (erg2).