DOCSLIB.ORG

Head and Neck Squamous Cell Carcinoma.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Ilda Patrícia Tavares da Silva Ribeiro Head and Neck Squamous Cell Carcinoma: integrating genomic, epigenetic and transcriptomic data - from bench to clinical applications Tese de doutoramento do Programa Interuniversitário de Doutoramento em Envelhecimento e Doenças Crónicas, orientada pela Senhora Professora Isabel Marques Carreira e pelo Senhor Professor Rui Manuel Reis e Coorientada pela Senhora Professora Joana Barbosa de Melo, o grau é conferido pelas Faculdade de Medicina da Universidade de Coimbra, Faculdade de Ciências Médicas da Universidade Nova de Lisboa e Escola de Ciências da Saúde da Universidade do Minho, e é apresentada à Faculdade de Medicina da Universidade de Coimbra. Julho 2017 Institutions and Funding The presented research study involved the following institutions and funding: i Publications The following original articles and abstracts have been published (or submitted) in peer-scientific journals, within the scope of the present work. Book Chapters Ilda P. Ribeiro, Joana B. Melo, Isabel M. Carreira (2017). High -Throughput Genomic Approaches for Head and Neck Cancer: Towards Molecular Biomarkers and Targeted Therapies, In: Head and Neck Cancer, Avid Science, Telangana, India, 2017. 2-31 Original articles (in chronological order) Published 1. Ilda P. Ribeiro, Francisco Marques, Leonor Barroso, Jorge Miguéis, Francisco Caramelo, André Santos, Maria J. Julião, Joana B. Melo, Isabel M. Carreira. Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor. Molecular Cytogenetics, 2017. 10(13):2-9 doi: 10.1186/s13039-017-0310-z (Chapter 3.4.3) 2. Ilda P. Ribeiro, Francisco Caramelo, Francisco Marques, Ana Domingues, Margarida Mesquita, Leonor Barroso, Hugo Prazeres, Maria J. Julião, Isabel P. Baptista, Artur Ferreira, Joana B. Melo, Isabel M. Carreira. WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report. Cellular Oncology, 2016. 39(6):573-582 doi: 10.1007/s13402-016-0293-5 (Chapter 3.1.3) 3. Ilda P. Ribeiro, Leonor Barroso, Francisco Marques, Joana B. Melo, Isabel M. Carreira. Early detection and personalized treatment in oral cancer: the impact of omics approaches. Molecular Cytogenetics, 2016. 9(85):1-7 doi: 10.1186/s13039-016-0293-1 iii 4. Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, João Pereira, Miguel Patrício, Hugo Prazeres, José Ferrão, Maria J. Julião, Miguel Castelo-Branco, Joana B. Melo, Isabel P. Baptista, Isabel M. Carreira. Genetic gains and losses in oral squamous cell carcinoma: impact on clinical management. Cellular Oncology, 2014. 37(1):29-39 doi:10.1007/s13402-013-0161-5 (Chapter 3.1.1) 5. Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, José Ferrão, Hugo Prazeres, Maria J. Julião, Widad Rifi, Suvi Savola, Joana B. Melo, Isabel P. Baptista, Isabel M. Carreira. Genetic imbalances detected by Multiplex Ligation-dependent Probe Amplification in a cohort of patients with oral squamous cell carcinoma - the first step towards clinical personalized medicine. Tumor Biology, 2014. 35 (5):4687-4695 doi: 10.1007/s13277-014-1614-9 (Chapter 3.1.2) In Press 1. Ilda P. Ribeiro, Francisco Marques, Leonor Barroso, Joana Rodrigues, Francisco Caramelo, Joana B. Melo, Isabel M. Carreira. Genomic profile of oral squamous cell carcinomas with an adjacent leukoplakia or with an erythroleukoplakia that evolved after the treatment of primary tumor: a report of two cases. Molecular Medicine Reports. (Chapter 3.4.1) 2. Ilda P. Ribeiro, Joana Rodrigues, Alexandra Mascarenhas, Nadezda Kosyakova, Francisco Caramelo, Thomas Liehr, Joana B. Melo, Isabel M. Carreira. Cytogenetic, genomic and epigenetic characterization of HSC-3 tongue cell line, with lymphnode metastasis. Journal of Oral Sciences. (Chapter 3.5.1) Submitted 1. Ilda P. Ribeiro, Francisco Caramelo, Luísa Esteves, Camila Oliveira, Francisco Marques, Leonor Barroso, Joana B. Melo, Isabel M. Carreira. Genomic and epigenetic signatures associated with survival rate in oral squamous cell carcinoma patients. (Chapter 3.1.4) iv 2. Ilda P. Ribeiro, Francisco Caramelo, Luísa Esteves, Joana Menoita, Francisco Marques, Leonor Barroso, Jorge Miguéis, Joana B. Melo, Isabel M. Carreira. Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients. (Chapter 3.2.1) 3. Ilda P. Ribeiro, Isabel M. Carreira, Thomas Liehr, Joana B. Melo. Chromosomal breaks and low copy repeat elements in head and neck squamous cell carcinoma. (Chapter 3.2.2) 4. Ilda P. Ribeiro, Luísa Esteves, Francisco Caramelo, Francisco Marques, Leonor Barroso, Joana B. Melo, Isabel M. Carreira. Expression of HIF3A, HOXA10 and LOX discriminates tumors of the tongue from the floor of the mouth. (Chapter 3.3.1) 5. Ilda P. Ribeiro, Leonor Barroso, Francisco Marques, André Santos, Francisco Caramelo, Maria J. Julião, Joana B. Melo, Isabel M. Carreira. Genomic and epigenetic characterization for the comparison of synchronous bilateral tongue squamous cell carcinomas - a case report. (Chapter 3.4.2) 6. Ilda P. Ribeiro, Joana M. Rodrigues, Alexandra Mascarenhas, Vanessa Marques, Nadezda Kosyakova, Francisco Caramelo, Maria J. Julião, Thomas Liehr, Joana B. Melo, Isabel M. Carreira. (Cyto)genomic and epigenetic characterization of BICR 10 cell line and three new established primary human head and neck squamous cell carcinoma cultures. (Chapter 3.5.2) Peer-Reviewed conference abstracts published on indexed journals 1. Isabel M. Carreira, Ilda P. Ribeiro, Susana I. Ferreira, Alexandra Mascarenhas, Joana Rodrigues, Vanessa Marques, Cláudia Pais, Francisco Marques, Joana B. Melo. From the establishment of primary culture cell v lines of oral squamous cell carcinoma to the identification of complex rearrangements. Molecular Cytogenetics, 2017. 10(Suppl1)2.20 2. Ilda P. Ribeiro, Francisco Caramelo, Francisco Marques, André Santos, Leonor Barroso, Margarida Mesquita, Teresa Lopes, Maria J. Julião, Artur Ferreira, Isabel P. Baptista, Joana B. Melo, Isabel M Carreira. Genomic classification of oral squamous cell carcinoma: the role of copy number alterations. European Journal of Human Genetics, Supplement. 2016; 24 (E-Supplement 1): 279 3. Isabel M. Carreira, Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, André Santos, Maria J. Julião, Isabel P. Baptista, Joana B. Melo. Oral squamous cell carcinoma: can the genes predict a second primary tumor? European Journal of Human Genetics, Supplement. 2016; 24 (E- Supplement 1): 295 4. Ilda P. Ribeiro, Francisco Marques, André Santos, Francisco Caramelo, Isabel P. Baptista, Joana B. Melo, Isabel M. Carreira. Novel regions of gain and loss on chromosome 11 detected in the oral squamous cell carcinoma. Revista Portuguesa de Pneumologia. 2016; 22 (Esp Cong 2):6 5. Ilda P. Ribeiro, Francisco Marques, André Santos, Joana Menoita, Isabel P. Baptista, Isabel M. Carreira, Joana B. Melo. Non-random genomic breakpoints in oral cancer: which characteristic sequence motifs are behind the breaks? Revista Portuguesa de Pneumologia. 2016; 22 (Esp Cong 2):13 6. Ilda P. Ribeiro, Francisco Caramelo, Francisco Marques, Ana Domingues, Alexandra Estevinho, Maria J. Julião, Artur Ferreira, Isabel P. Baptista, Joana B. Melo, Isabel M. Carreira. From oral cancer genetic and epigenetic alterations to clinical outcome prediction. European Journal of Human Genetics. 2015; (Supplement 1): 260 7. Ilda P. Ribeiro, Ana Cainço, Francisco Marques, Francisco Caramelo, Alexandra Estevinho, Maria J. Julião, Joana B. Melo, Artur Ferreira, Isabel P. Baptista, Isabel M. Carreira. Decoding genetic and epigenetic signatures in oral squamous cell carcinoma. Revista Portuguesa de Pneumologia. 2015. 21 (Esp Cong 1):4 vi 8. Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, Susana I. Ferreira, Luís M. Pires, Joana Rodrigues, Maria J. Julião, Joana B. Melo, Artur Ferreira, Isabel P. Baptista, Isabel M. Carreira. Genome-wide copy number analysis in oral squamous cell carcinoma. Revista Portuguesa de Pneumologia. 2015. 21 (Esp Cong 1):9 9. Ilda P. Ribeiro, Francisco Marques, Susana I. Ferreira, Luís M. Pires, Francisco Caramelo, Maria J. Julião, Joana B. Melo, Isabel P. Baptista, Isabel M. Carreira. The contribution of array-CGH to reveal genomic biomarkers for oral cancer. Revista Portuguesa de Pneumologia. 2014. 20:2-3 10. Ilda P. Ribeiro, Francisco Marques, Francisco Caramelo, José Ferrão, Maria J. Julião, Joana B. Melo, Isabel P. Baptista, Isabel M. Carreira. Genetic profile of oral cancer as a valuable ally for clinicians. Revista Portuguesa de Pneumologia. 2014. 20:10-11 11. Francisco Marques, Ilda P. Ribeiro, Hugo Prazeres, Maria J. Julião, Isabel P. Baptista, Joana B. Melo, Isabel M. Carreira. HPV and head and neck cancer: guilty or not guilty? Revista Portuguesa de Pneumologia. 2014. 20:11 12. Francisco Marques, Ilda P. Ribeiro, Susana I. Ferreira, José Ferrão, Maria J. Julião, Isabel P. Baptista, Joana B. Melo, Isabel M. Carreira. Head and neck cancer: a heterogeneous disease? Revista Portuguesa de Pneumologia. 2014. 20:11-12 Conference abstract published in conference proceedings 1. Ilda P. Ribeiro, Leonor Barroso, Francisco Marques, André Santos, Francisco Caramelo, Maria J. Julião, Joana B. Melo, Isabel M. Carreira. One patient and two synchronous tongue tumors: how genes help to discriminate bilateral carcinomas? Livro de Resumos 20ª Reunião Anual da Sociedade Portuguesa de Genética Humana, Fundação Bissaya Barreto, Coimbra (2016). pp129 vii 2. Ilda P. Ribeiro, André Santos, Francisco
Recommended publications
  • Regulation and Dysregulation of Chromosome Structure in Cancer

    Regulation and Dysregulation of Chromosome Structure in Cancer

    Regulation and Dysregulation of Chromosome Structure in Cancer The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Hnisz, Denes et al. “Regulation and Dysregulation of Chromosome Structure in Cancer.” Annual Review of Cancer Biology 2, 1 (March 2018): 21–40 © 2018 Annual Reviews As Published https://doi.org/10.1146/annurev-cancerbio-030617-050134 Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/117286 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike Detailed Terms http://creativecommons.org/licenses/by-nc-sa/4.0/ Regulation and dysregulation of chromosome structure in cancer Denes Hnisz1*, Jurian Schuijers1, Charles H. Li1,2, Richard A. Young1,2* 1 Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA 2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA * Corresponding authors Corresponding Authors: Denes Hnisz Whitehead Institute for Biomedical Research 455 Main Street Cambridge, MA 02142 Tel: (617) 258-7181 Fax: (617) 258-0376 [email protected] Richard A. Young Whitehead Institute for Biomedical Research 455 Main Street Cambridge, MA 02142 Tel: (617) 258-5218 Fax: (617) 258-0376 [email protected] 1 Summary Cancer arises from genetic alterations that produce dysregulated gene expression programs. Normal gene regulation occurs in the context of chromosome loop structures called insulated neighborhoods, and recent studies have shown that these structures are altered and can contribute to oncogene dysregulation in various cancer cells. We review here the types of genetic and epigenetic alterations that influence neighborhood structures and contribute to gene dysregulation in cancer, present models for insulated neighborhoods associated with the most prominent human oncogenes, and discuss how such models may lead to further advances in cancer diagnosis and therapy.
  • A Genome-Wide Study of Blood Pressure in African Americans Accounting for Gene-Smoking Interaction Jacquelyn Y

    A Genome-Wide Study of Blood Pressure in African Americans Accounting for Gene-Smoking Interaction Jacquelyn Y

    A Genome-wide study of blood pressure in African Americans accounting for gene-smoking interaction Jacquelyn Y. Taylor, Yale University Karen Schwander, Washington University in St. Louis Sharon L. R. Kardia, University of Michigan Donna Arnett, University of Alabama, Birmingham Jingjing Liang, Case Western Reserve University Steven C. Hunt, University of Utah D.C. Rao, Washington University in St. Louis Yan Sun, Emory University Journal Title: Scientific Reports Volume: Volume 6 Publisher: Nature Publishing Group | 2016-01-11, Pages 18812-18812 Type of Work: Article | Final Publisher PDF Publisher DOI: 10.1038/srep18812 Permanent URL: https://pid.emory.edu/ark:/25593/rhb37 Final published version: http://dx.doi.org/10.1038/srep18812 Copyright information: © 2016, Macmillan Publishers Limited This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). Accessed September 29, 2021 11:39 AM EDT www.nature.com/scientificreports OPEN A Genome-wide study of blood pressure in African Americans accounting for gene-smoking Received: 15 January 2015 Accepted: 09 November 2015 interaction Published: 11 January 2016 Jacquelyn Y. Taylor1, Karen Schwander2, Sharon L. R. Kardia3 & Donna Arnett4, Jingjing Liang5 Steven C. Hunt6, D.C. Rao2 & Yan V. Sun7,8 Cigarette smoking has been shown to be a health hazard. In addition to being considered a negative lifestyle behavior, studies have shown that cigarette smoking has been linked to genetic underpinnings of hypertension. Because African Americans have the highest incidence and prevalence of hypertension, we examined the joint effect of genetics and cigarette smoking on health among this understudied population.
  • The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease

    The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease

    The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease by Sepehr Ehsani A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Laboratory Medicine and Pathobiology University of Toronto © Copyright by Sepehr Ehsani 2012 The Significance of the Evolutionary Relationship of Prion Proteins and ZIP Transporters in Health and Disease Sepehr Ehsani Doctor of Philosophy Department of Laboratory Medicine and Pathobiology University of Toronto 2012 Abstract The cellular prion protein (PrPC) is unique amongst mammalian proteins in that it not only has the capacity to aggregate (in the form of scrapie PrP; PrPSc) and cause neuronal degeneration, but can also act as an independent vector for the transmission of disease from one individual to another of the same or, in some instances, other species. Since the discovery of PrPC nearly thirty years ago, two salient questions have remained largely unanswered, namely, (i) what is the normal function of the cellular protein in the central nervous system, and (ii) what is/are the factor(s) involved in the misfolding of PrPC into PrPSc? To shed light on aspects of these questions, we undertook a discovery-based interactome investigation of PrPC in mouse neuroblastoma cells (Chapter 2), and among the candidate interactors, identified two members of the ZIP family of zinc transporters (ZIP6 and ZIP10) as possessing a PrP-like domain. Detailed analyses revealed that the LIV-1 subfamily of ZIP transporters (to which ZIPs 6 and 10 belong) are in fact the evolutionary ancestors of prions (Chapter 3).
  • Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma

    Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma

    Anatomy and Pathology Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma Sarah L. Lake,1 Sarah E. Coupland,1 Azzam F. G. Taktak,2 and Bertil E. Damato3 PURPOSE. To detect deletions and loss of heterozygosity of disease is fatal in 92% of patients within 2 years of diagnosis. chromosome 3 in a rare subset of fatal, disomy 3 uveal mela- Clinical and histopathologic risk factors for UM metastasis noma (UM), undetectable by fluorescence in situ hybridization include large basal tumor diameter (LBD), ciliary body involve- (FISH). ment, epithelioid cytomorphology, extracellular matrix peri- ϩ ETHODS odic acid-Schiff-positive (PAS ) loops, and high mitotic M . Multiplex ligation-dependent probe amplification 3,4 5 (MLPA) with the P027 UM assay was performed on formalin- count. Prescher et al. showed that a nonrandom genetic fixed, paraffin-embedded (FFPE) whole tumor sections from 19 change, monosomy 3, correlates strongly with metastatic death, and the correlation has since been confirmed by several disomy 3 metastasizing UMs. Whole-genome microarray analy- 3,6–10 ses using a single-nucleotide polymorphism microarray (aSNP) groups. Consequently, fluorescence in situ hybridization were performed on frozen tissue samples from four fatal dis- (FISH) detection of chromosome 3 using a centromeric probe omy 3 metastasizing UMs and three disomy 3 tumors with Ͼ5 became routine practice for UM prognostication; however, 5% years’ metastasis-free survival. to 20% of disomy 3 UM patients unexpectedly develop metas- tases.11 Attempts have therefore been made to identify the RESULTS. Two metastasizing UMs that had been classified as minimal region(s) of deletion on chromosome 3.12–15 Despite disomy 3 by FISH analysis of a small tumor sample were found these studies, little progress has been made in defining the key on MLPA analysis to show monosomy 3.
  • Universidade Estadual De Campinas Instituto De Biologia

    Universidade Estadual De Campinas Instituto De Biologia

    UNIVERSIDADE ESTADUAL DE CAMPINAS INSTITUTO DE BIOLOGIA VERÔNICA APARECIDA MONTEIRO SAIA CEREDA O PROTEOMA DO CORPO CALOSO DA ESQUIZOFRENIA THE PROTEOME OF THE CORPUS CALLOSUM IN SCHIZOPHRENIA CAMPINAS 2016 1 VERÔNICA APARECIDA MONTEIRO SAIA CEREDA O PROTEOMA DO CORPO CALOSO DA ESQUIZOFRENIA THE PROTEOME OF THE CORPUS CALLOSUM IN SCHIZOPHRENIA Dissertação apresentada ao Instituto de Biologia da Universidade Estadual de Campinas como parte dos requisitos exigidos para a obtenção do Título de Mestra em Biologia Funcional e Molecular na área de concentração de Bioquímica. Dissertation presented to the Institute of Biology of the University of Campinas in partial fulfillment of the requirements for the degree of Master in Functional and Molecular Biology, in the area of Biochemistry. ESTE ARQUIVO DIGITAL CORRESPONDE À VERSÃO FINAL DA DISSERTAÇÃO DEFENDIDA PELA ALUNA VERÔNICA APARECIDA MONTEIRO SAIA CEREDA E ORIENTADA PELO DANIEL MARTINS-DE-SOUZA. Orientador: Daniel Martins-de-Souza CAMPINAS 2016 2 Agência(s) de fomento e nº(s) de processo(s): CNPq, 151787/2F2014-0 Ficha catalográfica Universidade Estadual de Campinas Biblioteca do Instituto de Biologia Mara Janaina de Oliveira - CRB 8/6972 Saia-Cereda, Verônica Aparecida Monteiro, 1988- Sa21p O proteoma do corpo caloso da esquizofrenia / Verônica Aparecida Monteiro Saia Cereda. – Campinas, SP : [s.n.], 2016. Orientador: Daniel Martins de Souza. Dissertação (mestrado) – Universidade Estadual de Campinas, Instituto de Biologia. 1. Esquizofrenia. 2. Espectrometria de massas. 3. Corpo caloso.
  • Sequencing-Based Computational Methods for Identifying Impactful Genomic Alterations in Cancers

    Sequencing-Based Computational Methods for Identifying Impactful Genomic Alterations in Cancers

    Sequencing-based computational methods for identifying impactful genomic alterations in cancers by Isaac Charles Joseph A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Computational Biology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Lior Pachter, Chair Professor Joseph Costello Associate Professor Haiyan Huang Professor Anthony Joseph Fall 2016 Sequencing-based computational methods for identifying impactful genomic alterations in cancers Copyright 2016 by Isaac Charles Joseph 1 Abstract Sequencing-based computational methods for identifying impactful genomic alterations in cancers by Isaac Charles Joseph Doctor of Philosophy in Computational Biology University of California, Berkeley Professor Lior Pachter, Chair Recent advances in collecting sequencing data from tumors is promising for both immediate individual patient treatment and investigation of cancer mechanisms. A resultant central goal is identifying changes in tumors that are impactful towards these ends. Here, we develop two tools to identify impactful changes at different levels. We develop both methods in the context of gliomas, a common form of brain cancer. Firstly, we develop and assess a tool for assessing the impact of fusion genes, a type of common mutation using RNA-sequencing data. We validate the tool by working with collaborators in The Cancer Genome Atlas. Secondly, we develop a tool for an overall assessment of patient outcome by integrating data from diverse sequencing platforms. We validate this tool using simulation, data from consortiums, and collaborators at UCSF. i To those that suffer It is you that have convinced me that there is something still worth fighting for in this world.
  • ABSTRACT MITCHELL III, ROBERT DRAKE. Global Human Health

    ABSTRACT MITCHELL III, ROBERT DRAKE. Global Human Health

    ABSTRACT MITCHELL III, ROBERT DRAKE. Global Human Health Risks for Arthropod Repellents or Insecticides and Alternative Control Strategies. (Under the direction of Dr. R. Michael Roe). Protein-coding genes and environmental chemicals. New paradigms for human health risk assessment of environmental chemicals emphasize the use of molecular methods and human-derived cell lines. In this study, we examined the effects of the insect repellent DEET (N, N-diethyl-m-toluamide) and the phenylpyrazole insecticide fipronil (fluocyanobenpyrazole) on transcript levels in primary human hepatocytes. These chemicals were tested individually and as a mixture. RNA-Seq showed that 100 µM DEET significantly increased transcript levels for 108 genes and lowered transcript levels for 64 genes and fipronil at 10 µM increased the levels of 2,246 transcripts and decreased the levels for 1,428 transcripts. Fipronil was 21-times more effective than DEET in eliciting changes, even though the treatment concentration was 10-fold lower for fipronil versus DEET. The mixture of DEET and fipronil produced a more than additive effect (levels increased for 3,017 transcripts and decreased for 2,087 transcripts). The transcripts affected in our treatments influenced various biological pathways and processes important to normal cellular functions. Long non-protein coding RNAs and environmental chemicals. While the synthesis and use of new chemical compounds is at an all-time high, the study of their potential impact on human health is quickly falling behind. We chose to examine the effects of two common environmental chemicals, the insect repellent DEET and the insecticide fipronil, on transcript levels of long non-protein coding RNAs (lncRNAs) in primary human hepatocytes.
  • Investigation of Candidate Genes and Mechanisms Underlying Obesity

    Investigation of Candidate Genes and Mechanisms Underlying Obesity

    Prashanth et al. BMC Endocrine Disorders (2021) 21:80 https://doi.org/10.1186/s12902-021-00718-5 RESEARCH ARTICLE Open Access Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules G. Prashanth1 , Basavaraj Vastrad2 , Anandkumar Tengli3 , Chanabasayya Vastrad4* and Iranna Kotturshetti5 Abstract Background: Obesity associated type 2 diabetes mellitus is a metabolic disorder ; however, the etiology of obesity associated type 2 diabetes mellitus remains largely unknown. There is an urgent need to further broaden the understanding of the molecular mechanism associated in obesity associated type 2 diabetes mellitus. Methods: To screen the differentially expressed genes (DEGs) that might play essential roles in obesity associated type 2 diabetes mellitus, the publicly available expression profiling by high throughput sequencing data (GSE143319) was downloaded and screened for DEGs. Then, Gene Ontology (GO) and REACTOME pathway enrichment analysis were performed. The protein - protein interaction network, miRNA - target genes regulatory network and TF-target gene regulatory network were constructed and analyzed for identification of hub and target genes. The hub genes were validated by receiver operating characteristic (ROC) curve analysis and RT- PCR analysis. Finally, a molecular docking study was performed on over expressed proteins to predict the target small drug molecules. Results: A total of 820 DEGs were identified between
  • Identification and Characterization of Tissue-Resident Memory T Cells in Humans Brahma Vencel Kumar

    Identification and Characterization of Tissue-Resident Memory T Cells in Humans Brahma Vencel Kumar

    Identification and characterization of tissue-resident memory T cells in humans Brahma Vencel Kumar Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2018 ©2017 Brahma Vencel Kumar All rights reserved ABSTRACT Identification and characterization of tissue-resident memory T cells in humans Brahma Vencel Kumar Memory T cells are critical for maintaining lifelong immunity by protecting against reinfection with previously encountered pathogens. In recent years, a subset of memory T cells termed tissue-resident memory T cells (TRM) has emerged as the primary mediator of protection at many tissue sites. Numerous studies in mice have demonstrated that TRM accelerate pathogen clearance compared with other subsets of memory T cells. The defining characteristic of TRM is that they are retained within tissues and do not circulate in the blood. The lack of TRM in blood has proved to be a barrier for investigating the role of TRM in healthy humans. As a result, there are many outstanding questions about TRM biology in humans, including which phenotypic markers identify TRM, if TRM represent a unique memory subset, as well as defining transcriptional and functional characteristics of this subset. Through a unique collaboration with the local organ procurement agency, we obtained samples from >15 tissue sites from healthy organ donors of all ages. We found that the surface marker CD69 was expressed by memory CD4 + and CD8 + T cells in multiple tissues including spleen and other lymphoid tissues, lung, and intestines, but not in blood, suggesting that this marker may identify TRM in human tissues.
  • Cellular and Molecular Signatures in the Disease Tissue of Early

    Cellular and Molecular Signatures in the Disease Tissue of Early

    Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of
  • DDEF1 Monoclonal Antibody (M01), Clone 2G7

    DDEF1 Monoclonal Antibody (M01), Clone 2G7

    Produktinformation Diagnostik & molekulare Diagnostik Laborgeräte & Service Zellkultur & Verbrauchsmaterial Forschungsprodukte & Biochemikalien Weitere Information auf den folgenden Seiten! See the following pages for more information! Lieferung & Zahlungsart Lieferung: frei Haus Bestellung auf Rechnung SZABO-SCANDIC Lieferung: € 10,- HandelsgmbH & Co KG Erstbestellung Vorauskassa Quellenstraße 110, A-1100 Wien T. +43(0)1 489 3961-0 Zuschläge F. +43(0)1 489 3961-7 [email protected] • Mindermengenzuschlag www.szabo-scandic.com • Trockeneiszuschlag • Gefahrgutzuschlag linkedin.com/company/szaboscandic • Expressversand facebook.com/szaboscandic DDEF1 monoclonal antibody (M01), clone 2G7 Catalog # : H00050807-M01 規格 : [ 100 ug ] List All Specification Application Image Product Mouse monoclonal antibody raised against a partial recombinant Western Blot (Cell lysate) Description: DDEF1. Immunogen: DDEF1 (NP_060952, 1030 a.a. ~ 1129 a.a) partial recombinant protein with GST tag. MW of the GST tag alone is 26 KDa. Sequence: VQSRDAIQKQASEDSNDLTPTLPETPVPLPRKINTGKNKVRRVKTIYDCQ ADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHILSD enlarge Western Blot (Cell lysate) Host: Mouse Reactivity: Human, Rat Isotype: IgG2a Kappa Quality Control Antibody Reactive Against Recombinant Protein. enlarge Testing: Western Blot (Recombinant protein) Immunofluorescence enlarge Sandwich ELISA (Recombinant Western Blot detection against Immunogen (36.74 KDa) . protein) Storage Buffer: In 1x PBS, pH 7.4 Storage Store at -20°C or lower. Aliquot to avoid repeated freezing
  • Integrative Analysis of Genomic Amplification-Dependent Expression

    Integrative Analysis of Genomic Amplification-Dependent Expression

    Oncogene (2020) 39:4118–4131 https://doi.org/10.1038/s41388-020-1279-3 ARTICLE Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression 1 1 1 2 2 Jichao He ● Ronan P. McLaughlin ● Lambert van der Beek ● Sander Canisius ● Lodewyk Wessels ● 3 3 3 1 1 Marcel Smid ● John W. M. Martens ● John A. Foekens ● Yinghui Zhang ● Bob van de Water Received: 26 September 2019 / Revised: 14 March 2020 / Accepted: 17 March 2020 / Published online: 31 March 2020 © The Author(s) 2020. This article is published with open access Abstract The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In this study, we have applied Analytical Multi- scale Identification of Recurring Events analysis and transcript quantification in the TNBC genome across 222 TNBC tumors and identified 138 candidate genes with positive correlation in copy number gain (CNG) and gene expression. siRNA-based 1234567890();,: 1234567890();,: loss-of-function screen of the candidate genes has validated EGFR, MYC, ASAP1, IRF2BP2, and CCT5 genes as drivers promoting proliferation in different TNBC cells. MYC, ASAP1, IRF2BP2, and CCT5 display frequent CNG and concurrent expression over 2173 breast cancer tumors (cBioPortal dataset). More frequently are MYC and ASAP1 amplified in TNBC tumors (>30%, n = 320). In particular, high expression of ASAP1, the ADP-ribosylation factor GTPase-activating protein, is significantly related to poor metastatic relapse-free survival of TNBC patients (n = 257, bc-GenExMiner).