Neuropathology
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Determining the Role of P53 Mutation in Human Breast
Determining the Role of p53 Mutation in Human Breast Cancer Progression Using Recombinant Mutant/Wild-Type p53 Heterozygous Human Mammary Epithelial Cell Culture Models Item Type text; Electronic Dissertation Authors Junk, Damian Jerome Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 28/09/2021 18:36:12 Link to Item http://hdl.handle.net/10150/193600 DETERMINING THE ROLE OF P53 MUTATION IN HUMAN BREAST CANCER PROGRESSION USING RECOMBINANT MUTANT/WILD-TYPE P53 HETEROZYGOUS HUMAN MAMMARY EPITHELIAL CELL CULTURE MODELS by Damian Jerome Junk _________________________ A Dissertation Submitted to the Faculty of the GRADUATE INTERDISCIPLINARY PROGRAM IN CANCER BIOLOGY In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2008 2 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Dissertation Committee, we certify that we have read the dissertation prepared by Damian Jerome Junk entitled Determining the Role of p53 Mutation in Human Breast Cancer Progression Using Recombinant Mutant/Wild-Type p53 Heterozygous Human Mammary Epithelial Cell Culture Models and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy _______________________________________________________________________ Date: 4/18/08 Bernard W. Futscher, Ph.D. _______________________________________________________________________ Date: 4/18/08 Anne E. Cress, Ph.D. _______________________________________________________________________ Date: 4/18/08 Jesse D. -
TITLE PAGE Oxidative Stress and Response to Thymidylate Synthase
Downloaded from molpharm.aspetjournals.org at ASPET Journals on October 2, 2021 -Targeted -Targeted 1 , University of of , University SC K.W.B., South Columbia, (U.O., Carolina, This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. -
140503 IPF Signatures Supplement Withfigs Thorax
Supplementary material for Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis Daryle J. DePianto1*, Sanjay Chandriani1⌘*, Alexander R. Abbas1, Guiquan Jia1, Elsa N. N’Diaye1, Patrick Caplazi1, Steven E. Kauder1, Sabyasachi Biswas1, Satyajit K. Karnik1#, Connie Ha1, Zora Modrusan1, Michael A. Matthay2, Jasleen Kukreja3, Harold R. Collard2, Jackson G. Egen1, Paul J. Wolters2§, and Joseph R. Arron1§ 1Genentech Research and Early Development, South San Francisco, CA 2Department of Medicine, University of California, San Francisco, CA 3Department of Surgery, University of California, San Francisco, CA ⌘Current address: Novartis Institutes for Biomedical Research, Emeryville, CA. #Current address: Gilead Sciences, Foster City, CA. *DJD and SC contributed equally to this manuscript §PJW and JRA co-directed this project Address correspondence to Paul J. Wolters, MD University of California, San Francisco Department of Medicine Box 0111 San Francisco, CA 94143-0111 [email protected] or Joseph R. Arron, MD, PhD Genentech, Inc. MS 231C 1 DNA Way South San Francisco, CA 94080 [email protected] 1 METHODS Human lung tissue samples Tissues were obtained at UCSF from clinical samples from IPF patients at the time of biopsy or lung transplantation. All patients were seen at UCSF and the diagnosis of IPF was established through multidisciplinary review of clinical, radiological, and pathological data according to criteria established by the consensus classification of the American Thoracic Society (ATS) and European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and the Latin American Thoracic Association (ALAT) (ref. 5 in main text). Non-diseased normal lung tissues were procured from lungs not used by the Northern California Transplant Donor Network. -
Curcumin Alters Gene Expression-Associated DNA Damage, Cell Cycle, Cell Survival and Cell Migration and Invasion in NCI-H460 Human Lung Cancer Cells in Vitro
ONCOLOGY REPORTS 34: 1853-1874, 2015 Curcumin alters gene expression-associated DNA damage, cell cycle, cell survival and cell migration and invasion in NCI-H460 human lung cancer cells in vitro I-TSANG CHIANG1,2, WEI-SHU WANG3, HSIN-CHUNG LIU4, SU-TSO YANG5, NOU-YING TANG6 and JING-GUNG CHUNG4,7 1Department of Radiation Oncology, National Yang‑Ming University Hospital, Yilan 260; 2Department of Radiological Technology, Central Taiwan University of Science and Technology, Taichung 40601; 3Department of Internal Medicine, National Yang‑Ming University Hospital, Yilan 260; 4Department of Biological Science and Technology, China Medical University, Taichung 404; 5Department of Radiology, China Medical University Hospital, Taichung 404; 6Graduate Institute of Chinese Medicine, China Medical University, Taichung 404; 7Department of Biotechnology, Asia University, Taichung 404, Taiwan, R.O.C. Received March 31, 2015; Accepted June 26, 2015 DOI: 10.3892/or.2015.4159 Abstract. Lung cancer is the most common cause of cancer CARD6, ID1 and ID2 genes, associated with cell survival and mortality and new cases are on the increase worldwide. the BRMS1L, associated with cell migration and invasion. However, the treatment of lung cancer remains unsatisfactory. Additionally, 59 downregulated genes exhibited a >4-fold Curcumin has been shown to induce cell death in many human change, including the DDIT3 gene, associated with DNA cancer cells, including human lung cancer cells. However, the damage; while 97 genes had a >3- to 4-fold change including the effects of curcumin on genetic mechanisms associated with DDIT4 gene, associated with DNA damage; the CCPG1 gene, these actions remain unclear. Curcumin (2 µM) was added associated with cell cycle and 321 genes with a >2- to 3-fold to NCI-H460 human lung cancer cells and the cells were including the GADD45A and CGREF1 genes, associated with incubated for 24 h. -
Differential Expression of 14-3-3 Isoforms in Human Alcoholic Brain
Published in final edited form as: Alcohol Clin Exp Res. 2011 June ; 35(6): 1041±1049. doi:10.1111/j.1530-0277.2011.01436.x. Differential expression of 14-3-3 isoforms in human alcoholic brain Rachel K. MacKay, M.MolBiol1, Natalie J. Colson, PhD1, Peter R. Dodd, PhD2, and Joanne M. Lewohl, PhD1 1Griffith Health Institute and School of Medical Sciences, Griffith University, Gold Coast Campus, Southport, Australia 2School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia Abstract Background—Neuropathological damage due to chronic alcohol abuse often results in impairment of cognitive function. The damage is particularly marked in the frontal cortex. The 14-3-3 protein family consists of 7 proteins, β, γ, ε, ζ, η, θ and σ, encoded by 7 distinct genes. They are highly conserved molecular chaperones with roles in regulation of metabolism, signal transduction, cell-cycle control, protein trafficking, and apoptosis. They may also play an important role in neurodegeneration in chronic alcoholism. Methods—We used Real-Time PCR to measure the expression of 14-3-3 mRNA transcripts in both the dorsolateral prefrontal cortex and motor cortex of human brains obtained at autopsy. Results—We found significantly lower 14-3-3β, γ and θ expression in both cortical areas of alcoholics; but no difference in 14-3-3η expression, and higher expression of 14-3-3σ, in both areas. Levels of 14-3-3ζ and ε transcripts were significantly lower only in alcoholic motor cortex. Conclusions—Altered 14-3-3 expression could contribute to synaptic dysfunction and altered neurotransmission in chronic alcohol misuse by human subjects. -
Evaluation of a New Method for Large-Scale and Gene-Targeted Next Generation DNA Sequencing in Nonmodel Species
University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 2013 Evaluation of a New Method for Large-Scale and Gene-targeted Next Generation DNA Sequencing in Nonmodel Species Ted Cosart The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Cosart, Ted, "Evaluation of a New Method for Large-Scale and Gene-targeted Next Generation DNA Sequencing in Nonmodel Species" (2013). Graduate Student Theses, Dissertations, & Professional Papers. 4133. https://scholarworks.umt.edu/etd/4133 This Dissertation is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact [email protected]. EVALUTATION OF A NEW METHOD FOR LARGE-SCALE AND GENE- TARGETED NEXT GENERATION DNA SEQUENCING IN NONMODEL SPECIES By Ted Cosart BA, University of Montana, Missoula, Montana, 1983 MS, University of Montana, Missoula, Montana, 2006 Dissertation presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Individualized, Interdisciplinary Graduate Program The University of Montana Missoula, Montana August, 2013 Approved by: Sandy Ross, Associate Dean of The Graduate School Graduate School Dr. Jesse Johnson, Co-Chair Computer Science Dr. Gordon Luikart, Co-Chair Flathead Biological Station Dr. Jeffrey Good Division of Biological Sciences Dr. William Holben Division of Biological Sciences Dr. Stephen Porcella Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases Dr. -
“Deciphering the Genetic Architecture of Prolificacy Related Traits in an Experimental Iberian X Meishan F2 Intercross”
UNIVERSITAT AUTÒNOMA DE BARCELONA Departament de Ciència Animal i dels Aliments Facultat de Veterinària “Deciphering the genetic architecture of prolificacy related traits in an experimental Iberian x Meishan F2 intercross” Ingrid Balcells Ortega PhD Thesis June, 2012 Supervisors: Armand Sánchez and Anna Tomás El Dr. Armand Sánchez Bonastre, catedràtic del Departament de Ciència Animal i dels Aliments de la Universitat Autònoma de Barcelona i la Dra. Anna Tomás Sangenís, investigadora en la Fundació d'Investigació Sanitària de les Illes Balears de Mallorca CERTIFIQUEN: Que l’Ingrid Balcells Ortega ha realitzat sota la seva direcció el treball de recerca “Deciphering the genetic architecture of prolificacy related traits in an experimental Iberian x Meishan F2 intercross” per a obtenir el grau de doctora per la Universitat Autònoma de Barcelona. Que aquest treball s’ha dut a terme al Departament de Ciència Animal i dels Aliments de la Facultat de Veterinària de la Universitat Autònoma de Barcelona. Bellaterra, 11 de Maig de 2012 Dr. Armand Sánchez Bonastre Dra. Anna Tomás Sangenís ACKNOWLEDGEMENTS Durant la realització d’aquesta tesi, han sigut moltes les persones que m’han acompanyat, tan a nivell professional com personal. Totes elles han aportat el seu granet de sorra per a que aquest projecte hagi tirat endavant i han fet que pugui recordar aquesta etapa amb un gran somriure a la cara. Als meus directors de tesi, el doctor Armand Sánchez i la doctora Anna Tomás. Per tota la confiança que heu dipositat en mi, per tots els coneixements que m’heu transmès, per donar-me copets a l’esquena en els moments de més desànim (sobretot en aquests últims mesos) i per mil coses més. -
WMC-79, a Potent Agent Against Colon Cancers, Induces Apoptosis Through a P53-Dependent Pathway
1617 WMC-79, a potent agent against colon cancers, induces apoptosis through a p53-dependent pathway Teresa Kosakowska-Cholody,1 Introduction 1 2 W. Marek Cholody, Anne Monks, The bisimidazoacridones are bifunctional antitumor Barbara A. Woynarowska,3 agents with strong selectivity against colon cancers (1, 2). and Christopher J. Michejda1 Recent studies of the effect of bisimidazoacridones on sensitive colon tumors cells revealed that these com- 1 Molecular Aspects of Drug Design, Structural Biophysics pounds act as cytostatic agents that completely arrest cell Laboratory, Center for Cancer Research; 2Screening Technologies Branch, Laboratory of Functional Genomics, Science Applications growth at G1 and G2-M check points but do not trigger International Corporation, National Cancer Institute at Frederick, cell death even at high concentrations (10 Amol/L; ref. 3). Frederick, Maryland; and 3Department of Radiation Oncology, The chemical structure of bisimidazoacridones is symmet- University of Texas Health Science Center, San Antonio, Texas rical in that it consists of two imidazoacridone moieties held together by linkers of various lengths and rigidities. Abstract We recently reported on the synthesis of unsymmetrical variants of the original bisimidazoacridones (4). WMC-79 WMC-79 is a synthetic agent with potent activity (Fig. 1), a compound consisting of an imidazoacridone against colon and hematopoietic tumors. In vitro, the moiety linked to a 3-nitronaphthalimide moiety via agent is most potent against colon cancer cells that 1,4-bispropenopiperazine linker, was found to be a potent carry the wild-type p53 tumor suppressor gene (HCT- but selective cytotoxic agent in a variety of tumor cell f 116 and RKO cells: GI50 <1 nmol/L, LC50 40 nmol/L). -
Novel Mutations in Breast Cancer Patients from Southwestern Colombia
Genetics and Molecular Biology 43, 4, e20190359 (2020) Copyright © 2020, Sociedade Brasileira de Genética. DOI: https://doi.org/10.1590/1678-4685-GMB-2019-0359 Short Communication Human and Medical Genetics Novel mutations in breast cancer patients from southwestern Colombia Melissa Solarte1,2 , Carolina Cortes-Urrea1,2, Nelson Rivera Franco2, Guillermo Barreto2 and Pedro A. Moreno1 1Universidad del Valle, School of Systems and Computing Engineering, Bioinformatics and Biocomputing Laboratory, Cali, Colombia. 2Universidad del Valle, Biology Department, Human molecular Genetic Laboratory, Cali, Colombia. Abstract Breast cancer is the leading cause of death by cancer among women in less developed regions. In Colombia, few pub- lished studies have applied next-generation sequencing technologies to evaluate the genetic factors related to breast cancer. This study characterized the exome of three patients with breast cancer from southwestern Colombia to identify likely pathogenic or disease-related DNA sequence variants in tumor cells. For this, the exomes of three tumor tissue samples from patients with breast cancer were sequenced. The bioinformatics analysis identified two pathogenic vari- ants in Fgfr4 and Nf1 genes, which are highly relevant for this type of cancer. Specifically, variant FGFR4-c.1162G>A predisposes individuals to a significantly accelerated progression of this pathology, while NF1-c.1915C>T negatively alters the encoded protein and should be further investigated to clarify the role of this variant in this neoplasia. More- over, 27 novel likely pathogenic variants were found and 10 genes showed alterations of pathological interest. These results suggest that the novel variants reported here should be further studied to elucidate their role in breast cancer. -
Evidence for the Role of Ywha in Mouse Oocyte Maturation
EVIDENCE FOR THE ROLE OF YWHA IN MOUSE OOCYTE MATURATION A thesis submitted To Kent State University in partial Fulfillment of the requirements for the Degree of Master of Science By Ariana Claire Detwiler August, 2015 © Copyright All rights reserved Except for previously published materials Thesis written by Ariana Claire Detwiler B.S., Pennsylvania State University, 2012 M.S., Kent State University, 2015 Approved by ___________________________________________________________ Douglas W. Kline, Professor, Ph.D., Department of Biological Sciences, Masters Advisor ___________________________________________________________ Laura G. Leff, Professor, PhD., Chair, Department of Biological Sciences ___________________________________________________________ James L. Blank, Professor, Dean, College of Arts and Sciences i TABLE OF CONTENTS List of Figures ……………………………………………………………………………………v List of Tables ……………………………………………………………………………………vii Acknowledgements …………………………………………………………………………….viii Abstract ……………………………………………………………………………………….....1 Chapter I Introduction…………………………………………………………………………………..2 1.1 Introduction …………………………………………………………………………..2 1.2 Ovarian Function ……………………………………………………………………..2 1.3 Oogenesis and Folliculogenesis ………………………………………………………3 1.4 Oocyte Maturation ……………………………………………………………………5 1.5 Maternal to Embryonic Messenger RNA Transition …………………………………8 1.6 Meiotic Spindle Formation …………………………………………………………...9 1.7 YWHA Isoforms and Oocyte Maturation …………………………………………...10 Aim…………………………………………………………………………………………..15 Chapter II Methods……………………………………………………………………………………...16 -
The Kinesin Spindle Protein Inhibitor Filanesib Enhances the Activity of Pomalidomide and Dexamethasone in Multiple Myeloma
Plasma Cell Disorders SUPPLEMENTARY APPENDIX The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma Susana Hernández-García, 1 Laura San-Segundo, 1 Lorena González-Méndez, 1 Luis A. Corchete, 1 Irena Misiewicz- Krzeminska, 1,2 Montserrat Martín-Sánchez, 1 Ana-Alicia López-Iglesias, 1 Esperanza Macarena Algarín, 1 Pedro Mogollón, 1 Andrea Díaz-Tejedor, 1 Teresa Paíno, 1 Brian Tunquist, 3 María-Victoria Mateos, 1 Norma C Gutiérrez, 1 Elena Díaz- Rodriguez, 1 Mercedes Garayoa 1* and Enrique M Ocio 1* 1Centro Investigación del Cáncer-IBMCC (CSIC-USAL) and Hospital Universitario-IBSAL, Salamanca, Spain; 2National Medicines Insti - tute, Warsaw, Poland and 3Array BioPharma, Boulder, Colorado, USA *MG and EMO contributed equally to this work ©2017 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2017.168666 Received: March 13, 2017. Accepted: August 29, 2017. Pre-published: August 31, 2017. Correspondence: [email protected] MATERIAL AND METHODS Reagents and drugs. Filanesib (F) was provided by Array BioPharma Inc. (Boulder, CO, USA). Thalidomide (T), lenalidomide (L) and pomalidomide (P) were purchased from Selleckchem (Houston, TX, USA), dexamethasone (D) from Sigma-Aldrich (St Louis, MO, USA) and bortezomib from LC Laboratories (Woburn, MA, USA). Generic chemicals were acquired from Sigma Chemical Co., Roche Biochemicals (Mannheim, Germany), Merck & Co., Inc. (Darmstadt, Germany). MM cell lines, patient samples and cultures. Origin, authentication and in vitro growth conditions of human MM cell lines have already been characterized (17, 18). The study of drug activity in the presence of IL-6, IGF-1 or in co-culture with primary bone marrow mesenchymal stromal cells (BMSCs) or the human mesenchymal stromal cell line (hMSC–TERT) was performed as described previously (19, 20). -
Crystal Structure of Human Profilaggrin S100 Domain And
ORIGINAL ARTICLE Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target Proteins Annexin II, Stratifin, and HSP27 Christopher G. Bunick1,2,6, Richard B. Presland3,4,6, Owen T. Lawrence3,5, David J. Pearton3,5, Leonard M. Milstone1 and Thomas A. Steitz2 The fused-type S100 protein profilaggrin and its proteolytic products including filaggrin are important in the formation of a normal epidermal barrier; however, the specific function of the S100 calcium-binding domain in profilaggrin biology is poorly understood. To explore its molecular function, we determined a 2.2 Å-resolution crystal structure of the N-terminal fused-type S100 domain of human profilaggrin with bound calcium ions. The profilaggrin S100 domain formed a stable dimer, which contained two hydrophobic pockets that provide a molecular interface for protein interactions. Biochemical and molecular approaches demonstrated that three proteins, annexin II/p36, stratifin/14-3-3 sigma, and heat shock protein 27, bind to the N-terminal domain of human profilaggrin; one protein (stratifin) co-localized with profilaggrin in the differentiating granular cell layer of human skin. Together, these findings suggest a model where the profilaggrin N-terminus uses calcium-dependent and calcium-independent protein–protein interactions to regulate its involvement in keratinocyte terminal differentiation and incorporation into the cornified cell envelope. Journal of Investigative Dermatology (2015) 135, 1801–1809; doi:10.1038/jid.2015.102; published online 9 April 2015 INTRODUCTION In all mammals examined, profilaggrin has four distinct Profilaggrin is an ~ 400 kDa human protein critical for normal domains: (1) a 92 amino acid N-terminal S100 fused-type skin barrier development.