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Metabolite systems profiling identifies exploitable weaknesses in retinoblastoma
, Ranjith Kumar Ravi Kumar, Brandon Nicolay, Omkar Mohite, Karthikeyan Sivaraman, Vikas Khetan, Pukhraj Rishi, Suganeswari Ganesan, Krishnakumar Subramanyan, Show More
Published in Wiley Blackwell
2019
PMID: 30417337
Volume: 593
   
Issue: 1
Pages: 23 - 41
Abstract

Retinoblastoma (RB) is a childhood eye cancer. Currently, chemotherapy, local therapy, and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint-based reconstruction and analysis approaches to identify and explain RB-specific survival strategies, which are RB tumor specific. Importantly, our model-specific secretion profile is also found in RB1-depleted human retinal cells in vitro and suggests that novel biomarkers involved in lipid metabolism may be important. Finally, RB-specific synthetic lethals have been predicted as lipid and nucleoside transport proteins that can aid in novel drug target development. © 2018 Federation of European Biochemical Societies

About the journal
JournalData powered by TypesetFEBS Letters
PublisherData powered by TypesetWiley Blackwell
ISSN00145793
Open AccessNo
Concepts (66)
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    4 AMINOBUTYRATE AMINOTRANSFERASE
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    Biological marker
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    Lipid
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    Long chain fatty acid
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    NUCLEOSIDE TRANSPORTER
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    ORNITHINE OXOACID AMINOTRANSFERASE
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    Nucleoside
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    RB1 PROTEIN, HUMAN
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    RETINOBLASTOMA BINDING PROTEIN
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    Tumor marker
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    UBIQUITIN PROTEIN LIGASE
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    Article
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    Biomass
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    Cancer model
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    Cancer survival
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    Child
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    Clinical article
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    Comparative study
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    Controlled study
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    Drug targeting
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    Fatty acid synthesis
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    Gene expression
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    Human
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    Human cell
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    Human tissue
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    In vitro study
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    LETHAL MUTATION
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    Lipid metabolism
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    LIPID TRANSPORT
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    Mathematical model
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    Metabolite
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    NUCLEOSIDE TRANSPORT
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    Preschool child
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    Priority journal
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    Protein analysis
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    RETINA CELL
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    Retinoblastoma
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    RNA EXTRACTION
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    RNA SEQUENCE
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    School child
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    Systems biology
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    Case control study
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    DISEASE EXACERBATION
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    Gene expression profiling
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    Gene expression regulation
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    Genetics
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    Metabolism
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    Metabolomics
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    Procedures
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    Sequence analysis
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    Theoretical model
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    Transport at the cellular level
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    Young adult
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    Biological transport
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    BIOMARKERS, TUMOR
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    Case-control studies
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    Child, preschool
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    DISEASE PROGRESSION
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    GENE EXPRESSION REGULATION, NEOPLASTIC
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    Humans
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    Models, theoretical
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    Nucleosides
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    RETINOBLASTOMA BINDING PROTEINS
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    SEQUENCE ANALYSIS, RNA
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    SYNTHETIC LETHAL MUTATIONS
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    UBIQUITIN-PROTEIN LIGASES