Alterations in Cerebrospinal Fluid Proteins in a Presymptomatic Primary Glioma Model
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{"title"=>"Alterations in Cerebrospinal Fluid Proteins in a Presymptomatic Primary Glioma Model", "type"=>"journal", "authors"=>[{"first_name"=>"John C.", "last_name"=>"Whitin", "scopus_author_id"=>"7003752518"}, {"first_name"=>"Taichang", "last_name"=>"Jang", "scopus_author_id"=>"7102425940"}, {"first_name"=>"Milton", "last_name"=>"Merchant", "scopus_author_id"=>"23995761200"}, {"first_name"=>"Tom T.S.", "last_name"=>"Yu", "scopus_author_id"=>"15833686400"}, {"first_name"=>"Kenneth", "last_name"=>"Lau", "scopus_author_id"=>"7401560119"}, {"first_name"=>"Benjamin", "last_name"=>"Recht", "scopus_author_id"=>"6602593952"}, {"first_name"=>"Harvey J.", "last_name"=>"Cohen", "scopus_author_id"=>"7402808868"}, {"first_name"=>"Lawrence", "last_name"=>"Recht", "scopus_author_id"=>"7005624473"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23185417", "doi"=>"10.1371/journal.pone.0049724", "issn"=>"19326203", "pui"=>"366105251", "isbn"=>"1932-6203", "sgr"=>"84869779517", "scopus"=>"2-s2.0-84869779517"}, "id"=>"b6b6276d-6c8a-3b0b-aa4b-4a6d25e0a757", "abstract"=>"BACKGROUND: Understanding the early relationship between brain tumor cells and their environment could lead to more sensitive biomarkers and new therapeutic strategies. We have been using a rodent model of neurocarcinogenesis in which all animals develop brain tumors by six months of age to establish two early landmarks in glioma development: the appearance of a nestin(+) cell at thirty days of age and the appearance of cellular hyperplasia between 60 and 120 days of age. We now report an assessment of the CSF proteome to determine the changes in protein composition that occur during this period.\\n\\nMATERIALS AND METHODS: Nestin(+) cell clusters and microtumors were assessed in 63 ethylnitrosourea-exposed rats on 30, 60, and 90 days of age. CSF was obtained from the cisterna magna from 101 exposed and control rats at 30, 60, and 90 days and then analyzed using mass spectrometry. Differentially expressed peaks were isolated and identified.\\n\\nRESULTS: Nestin(+) cells were noted in all ethylnitrosourea-exposed rats assessed pathologically. Small microtumors were noted in 0%, 18%, and 67% of 30-, 60-, and 90-day old rats, respectively (p<0.05, Chi square). False Discovery Rate analysis of peak intensities showed that the number of true discoveries with p<0.05 increased markedly with increasing age. Isolation and identification of highly differentially detected proteins at 90 days of age revealed increases in albumin and a fragment of α1 macroglobulin and alterations in glutathionylated transthyretin.\\n\\nCONCLUSIONS: The presence of increased albumin, fragments of cerebrospinal fluid proteins, and glutathione breakdown in temporal association with the development of cellular hyperplasia, suggests that, similar to many other systemic cancers, inflammation and oxidative stress is playing an important early role in the host's response to brain tumor development and may be involved in affecting the early growth of brain tumor.", "link"=>"http://www.mendeley.com/research/alterations-cerebrospinal-fluid-proteins-presymptomatic-primary-glioma-model", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>4, "Neuroscience"=>2, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Russia"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/540779"], "description"=>"<p>This figure plots the average cross-validation error as the number of markers are varied. Each data point was created by running the LASSO on 80% of the data set and recording the prediction error on the held out 20%. This procedure was repeated 1000 times, and the average error is then plotted on the graph. The lowest error is achieved using a classifier with 5 markers.</p>", "links"=>[], "tags"=>["biomarkers", "lasso"], "article_id"=>211270, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.g008", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cross_validation_error_versus_number_of_biomarkers_in_LASSO_analysis_/211270", "title"=>"Cross-validation error versus number of biomarkers in LASSO analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-19 00:21:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/539959"], "description"=>"<p>(A) Characteristic appearance of nestin+ cells that arise in locations commonly noted to harbor tumors at later stages. These usually appear as either a single or more nestin+ cells that arise on a bland background that appears normal on H&E staining. These clusters sometimes can include dozens of cells (B). (C) Small microtumor arising in the external capsule of the <i>corpus callosum</i> (CC). These tumors are hypercellular and apparent on H & E and contain a significant fraction of cells that do not express neural markers.</p>", "links"=>[], "tags"=>["cells", "glioma", "enu"], "article_id"=>210438, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.g001", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nestin_cells_in_glioma_development_after_in_utero_ENU_exposure_/210438", "title"=>"Nestin<sup>+</sup> cells in glioma development after <i>in utero</i> ENU exposure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-19 00:07:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/540848"], "description"=>"<p>Peaks in bold type are z = 1. Peaks in italics are aliases (z = 2 or 3, or dimers) of the indicated protein.</p>", "links"=>[], "tags"=>["mann-whitney"], "article_id"=>211337, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.t002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Peaks_with_low_Mann_Whitney_U_test_and_low_local_FDR_/211337", "title"=>"Peaks with low Mann-Whitney <i>U</i> test and low local FDR.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-19 00:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/540885"], "description"=>"<p>LASSO Analysis.</p>", "links"=>[], "tags"=>["oncology", "pathology", "Biochemistry"], "article_id"=>211370, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.t003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LASSO_Analysis_/211370", "title"=>"LASSO Analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-19 00:22:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/540493"], "description"=>"<p>The SELDI peak intensities for the 3493 peak in P90 CSF are shown for both A) unfractionated CSF (n = 23 for Ctl, n = 22 for ENU, mean±SEM, Mann Whitney <i>U</i> test); and B) F×1 of anion exchange-fractionated CSF (n = 20 for Ctl, n = 20 for ENU, mean±SEM, Mann-Whitney <i>U</i> test).</p>", "links"=>[], "tags"=>["intensities"], "article_id"=>210990, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.g006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SELDI_peak_intensities_of_3493_/210990", "title"=>"SELDI peak intensities of 3493.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-19 00:16:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/290505", "https://ndownloader.figshare.com/files/290552", "https://ndownloader.figshare.com/files/290617", "https://ndownloader.figshare.com/files/290670", "https://ndownloader.figshare.com/files/290752"], "description"=>"<div><h3>Background</h3><p>Understanding the early relationship between brain tumor cells and their environment could lead to more sensitive biomarkers and new therapeutic strategies. We have been using a rodent model of neurocarcinogenesis in which all animals develop brain tumors by six months of age to establish two early landmarks in glioma development: the appearance of a nestin<sup>+</sup> cell at thirty days of age and the appearance of cellular hyperplasia between 60 and 120 days of age. We now report an assessment of the CSF proteome to determine the changes in protein composition that occur during this period.</p> <h3>Materials and Methods</h3><p>Nestin<sup>+</sup> cell clusters and microtumors were assessed in 63 ethylnitrosourea-exposed rats on 30, 60, and 90 days of age. CSF was obtained from the cisterna magna from 101 exposed and control rats at 30, 60, and 90 days and then analyzed using mass spectrometry. Differentially expressed peaks were isolated and identified.</p> <h3>Results</h3><p>Nestin<sup>+</sup> cells were noted in all ethylnitrosourea-exposed rats assessed pathologically. Small microtumors were noted in 0%, 18%, and 67% of 30-, 60-, and 90-day old rats, respectively (<em>p</em><0.05, Chi square). False Discovery Rate analysis of peak intensities showed that the number of true discoveries with p<0.05 increased markedly with increasing age. Isolation and identification of highly differentially detected proteins at 90 days of age revealed increases in albumin and a fragment of α1 macroglobulin and alterations in glutathionylated transthyretin.</p> <h3>Conclusions</h3><p>The presence of increased albumin, fragments of cerebrospinal fluid proteins, and glutathione breakdown in temporal association with the development of cellular hyperplasia, suggests that, similar to many other systemic cancers, inflammation and oxidative stress is playing an important early role in the host’s response to brain tumor development and may be involved in affecting the early growth of brain tumor.</p> </div>", "links"=>[], "tags"=>["alterations", "cerebrospinal", "proteins", "presymptomatic", "glioma", "model"], "article_id"=>117200, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049724.s001", "https://dx.doi.org/10.1371/journal.pone.0049724.s002", "https://dx.doi.org/10.1371/journal.pone.0049724.s003", "https://dx.doi.org/10.1371/journal.pone.0049724.s004", "https://dx.doi.org/10.1371/journal.pone.0049724.s005"], "stats"=>{"downloads"=>35, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Alterations_in_Cerebrospinal_Fluid_Proteins_in_a_Presymptomatic_Primary_Glioma_Model__/117200", "title"=>"Alterations in Cerebrospinal Fluid Proteins in a Presymptomatic Primary Glioma Model", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-11-19 02:00:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/540151"], "description"=>"<p>The number of tumor nodules is significantly greater at P90 (67%) than P60 (18%) and P30 (0%) (<i>p</i><0.001, Chi-square).</p>", "links"=>[], "tags"=>["nests", "hyperplastic", "microtumors"], "article_id"=>210641, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Numbers_of_nests_and_hyperplastic_microtumors_as_a_function_of_age_/210641", "title"=>"Numbers of nests and hyperplastic microtumors as a function of age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-19 00:10:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/540639"], "description"=>"<p>(A) Spectrum of transthyretin peaks. (B–E). Peak intensities of unmodified, cysteinylated, -cys-gly and glutathionylated transthyretin, respectively. (F) Sum of the peak intensities of unmodified, cyteinylated, -cys-gly and glutathionylated transthyretins. (n = 23 for Ctl, n = 22 for ENU for B–F, mean±SEM, Mann-Whitney <i>U</i> test).</p>", "links"=>[], "tags"=>["amounts", "transthyretin", "fragments", "enu-exposed", "rats", "compared"], "article_id"=>211122, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_the_amounts_of_transthyretin_fragments_in_ENU_exposed_rats_compared_with_control_rats_at_P90_/211122", "title"=>"Changes in the amounts of transthyretin fragments in ENU-exposed rats compared with control rats at P90.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-19 00:18:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/540923"], "description"=>"<p>247 peaks analyzed.</p>", "links"=>[], "tags"=>["fdr"], "article_id"=>211412, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mann_Whitney_U_test_results_with_Local_FDR_analysis_/211412", "title"=>"Mann-Whitney <i>U</i> test results with Local FDR analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-19 00:23:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/540413"], "description"=>"<p>This relationship was noted for both ENU-exposed and control rats at all ages. The linear regression correlation coefficient was R = −0.945.</p>", "links"=>[], "tags"=>["albumin", "pgd2s"], "article_id"=>210902, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.g005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relationship_between_albumin_and_PGD2S_peak_intensities_/210902", "title"=>"Relationship between albumin and PGD2S peak intensities.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-19 00:15:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/540221"], "description"=>"<p>The top line (+) indicates the number of discoveries observed at each <i>p</i>-value up to 0.05. The bottom line (o) represents the average number of discoveries observed at each <i>p</i> value when the data are permuted 100 times.</p>", "links"=>[], "tags"=>["discoveries"], "article_id"=>210711, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.g003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_number_of_total_discoveries_relative_to_global_false_discoveries_as_a_function_of_increasing_age_/210711", "title"=>"The number of total discoveries relative to global false discoveries as a function of increasing age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-19 00:11:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/540296"], "description"=>"<p>Left panel represents the SELDI peak intensities (µA signal) (n = 23 for Ctl, n = 22 for ENU, mean±SEM, Mann-Whitney <i>U</i> test). Right panel represents results of Western blots, measured using densitometry (units related to the integration of absorbance by the band on x-ray film, with the integration area fixed to be the same size for all lanes) (n = 7 for Ctl, n = 7 for ENU, mean±SEM, Mann-Whitney <i>U</i> test).</p>", "links"=>[], "tags"=>["levels", "p90", "enu-exposed", "csf", "seldi"], "article_id"=>210776, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["John C. Whitin", "Taichang Jang", "Milton Merchant", "Tom T-S. Yu", "Kenneth Lau", "Benjamin Recht", "Harvey J. Cohen", "Lawrence Recht"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049724.g004", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Albumin_levels_in_P90_ENU_exposed_rat_CSF_by_SELDI_peak_intensity_and_Western_blotting_/210776", "title"=>"Albumin levels in P90 ENU-exposed rat CSF by SELDI peak intensity and Western blotting.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-19 00:12:56"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2015", "month"=>"11"}
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