Alterations in cerebrospinal fluid proteins in a presymptomatic primary glioma model
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...
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| Veröffentlicht in: | PloS one 2012-11, Vol.7 (11), p.e49724 |
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| creator | Whitin, John C Jang, Taichang Merchant, Milton Yu, Tom T-S Lau, Kenneth Recht, Benjamin Cohen, Harvey J Recht, Lawrence |
| description | 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.
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.
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 |
| doi_str_mv | 10.1371/journal.pone.0049724 |
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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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0049724</identifier><identifier>PMID: 23185417</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Albumin ; Animals ; Arthritis ; Biology ; Biomarkers ; Biomarkers - metabolism ; Brain ; Brain - pathology ; Brain cancer ; Brain Neoplasms - cerebrospinal fluid ; Brain Neoplasms - metabolism ; Brain tumors ; Cerebrospinal fluid ; Cerebrospinal fluid proteins ; Cerebrospinal Fluid Proteins - metabolism ; Chi-square test ; Disease Models, Animal ; Ethylnitrosourea - pharmacology ; Exposure ; Gene Expression Regulation, Neoplastic ; Glioma ; Glioma - cerebrospinal fluid ; Glioma - metabolism ; Gliomas ; Glutathione ; Glutathione - metabolism ; Health aspects ; Hyperplasia ; Intermediate Filament Proteins - biosynthesis ; Mass spectrometry ; Mass spectroscopy ; Medicine ; Nerve Tissue Proteins - biosynthesis ; Nestin ; Neurology ; NMR ; Nuclear magnetic resonance ; Oxidative stress ; Pediatrics ; Protein composition ; Protein expression ; Proteins ; Proteome ; Proteomes ; Proteomics ; Proteomics - methods ; Rats ; Rats, Sprague-Dawley ; Rodents ; Studies ; Time Factors ; Transthyretin ; Tumor cells ; Tumors</subject><ispartof>PloS one, 2012-11, Vol.7 (11), p.e49724</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Whitin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Whitin et al 2012 Whitin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-2ab523dfecd72a83466291e6b06c28c2edd7cb8e6130f2ff62d87bac027e982b3</citedby><cites>FETCH-LOGICAL-c758t-2ab523dfecd72a83466291e6b06c28c2edd7cb8e6130f2ff62d87bac027e982b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501526/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501526/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23185417$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rota, Rossella</contributor><creatorcontrib>Whitin, John C</creatorcontrib><creatorcontrib>Jang, Taichang</creatorcontrib><creatorcontrib>Merchant, Milton</creatorcontrib><creatorcontrib>Yu, Tom T-S</creatorcontrib><creatorcontrib>Lau, Kenneth</creatorcontrib><creatorcontrib>Recht, Benjamin</creatorcontrib><creatorcontrib>Cohen, Harvey J</creatorcontrib><creatorcontrib>Recht, Lawrence</creatorcontrib><title>Alterations in cerebrospinal fluid proteins in a presymptomatic primary glioma model</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.
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.</description><subject>Age</subject><subject>Albumin</subject><subject>Animals</subject><subject>Arthritis</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Brain</subject><subject>Brain - pathology</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - cerebrospinal fluid</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain tumors</subject><subject>Cerebrospinal fluid</subject><subject>Cerebrospinal fluid proteins</subject><subject>Cerebrospinal Fluid Proteins - metabolism</subject><subject>Chi-square test</subject><subject>Disease Models, Animal</subject><subject>Ethylnitrosourea - pharmacology</subject><subject>Exposure</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glioma</subject><subject>Glioma - cerebrospinal fluid</subject><subject>Glioma - metabolism</subject><subject>Gliomas</subject><subject>Glutathione</subject><subject>Glutathione - metabolism</subject><subject>Health aspects</subject><subject>Hyperplasia</subject><subject>Intermediate Filament Proteins - biosynthesis</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medicine</subject><subject>Nerve Tissue Proteins - biosynthesis</subject><subject>Nestin</subject><subject>Neurology</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Oxidative stress</subject><subject>Pediatrics</subject><subject>Protein composition</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Proteome</subject><subject>Proteomes</subject><subject>Proteomics</subject><subject>Proteomics - methods</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Studies</subject><subject>Time Factors</subject><subject>Transthyretin</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLguDFjPlok_RGGBY_BhYWdPU2pMnJTIa0GZNW3H9vZqe7TEFBctHk5HnfnB7eoniJ0RJTjt_vwhh75Zf70MMSoarhpHpUnOOGkgUjiD4-2Z8Vz1LaIVRTwdjT4oxQLOoK8_PiZuUHiGpwoU-l60sNEdoY0t5l79L60ZlyH8MA7niv8gnSbbcfQpdVOh9dp-JtufEuV8ouGPDPiydW-QQvpu9F8f3Tx5vLL4ur68_ry9XVQvNaDAui2ppQY0EbTpSgFWOkwcBaxDQRmoAxXLcCGKbIEmsZMYK3SiPCoRGkpRfF66Pv3ockp4EkiSlhvCK8wplYHwkT1E5OvcqgnLwrhLiRKubf8CCtpUy12FjW5NEwLFgjdMVFw2lTAxxe-zC9NrYdGA39EJWfmc5vereVm_BL0hrhmrBs8GYyiOHnCGn4R8sTtVG5K9fbkM1055KWq4pzxKoGVZla_oXKy0DndI6Edbk-E7ybCTIzwO9ho8aU5Prb1_9nr3_M2bcn7BaUH7Yp-PEuUXOwOoI6xytFsA-Tw0geEn0_DXlItJwSnWWvTqf-ILqPMP0D_EDx1Q</recordid><startdate>20121119</startdate><enddate>20121119</enddate><creator>Whitin, John C</creator><creator>Jang, Taichang</creator><creator>Merchant, Milton</creator><creator>Yu, Tom T-S</creator><creator>Lau, Kenneth</creator><creator>Recht, Benjamin</creator><creator>Cohen, Harvey J</creator><creator>Recht, Lawrence</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20121119</creationdate><title>Alterations in cerebrospinal fluid proteins in a presymptomatic primary glioma model</title><author>Whitin, John C ; Jang, Taichang ; Merchant, Milton ; Yu, Tom T-S ; Lau, Kenneth ; Recht, Benjamin ; Cohen, Harvey J ; Recht, Lawrence</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-2ab523dfecd72a83466291e6b06c28c2edd7cb8e6130f2ff62d87bac027e982b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Age</topic><topic>Albumin</topic><topic>Animals</topic><topic>Arthritis</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biomarkers - 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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.
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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23185417</pmid><doi>10.1371/journal.pone.0049724</doi><tpages>e49724</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-11, Vol.7 (11), p.e49724 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1326742741 |
| source | MEDLINE; EZB Free E-Journals; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Age Albumin Animals Arthritis Biology Biomarkers Biomarkers - metabolism Brain Brain - pathology Brain cancer Brain Neoplasms - cerebrospinal fluid Brain Neoplasms - metabolism Brain tumors Cerebrospinal fluid Cerebrospinal fluid proteins Cerebrospinal Fluid Proteins - metabolism Chi-square test Disease Models, Animal Ethylnitrosourea - pharmacology Exposure Gene Expression Regulation, Neoplastic Glioma Glioma - cerebrospinal fluid Glioma - metabolism Gliomas Glutathione Glutathione - metabolism Health aspects Hyperplasia Intermediate Filament Proteins - biosynthesis Mass spectrometry Mass spectroscopy Medicine Nerve Tissue Proteins - biosynthesis Nestin Neurology NMR Nuclear magnetic resonance Oxidative stress Pediatrics Protein composition Protein expression Proteins Proteome Proteomes Proteomics Proteomics - methods Rats Rats, Sprague-Dawley Rodents Studies Time Factors Transthyretin Tumor cells Tumors |
| title | Alterations in cerebrospinal fluid proteins in a presymptomatic primary glioma model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T07%3A33%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alterations%20in%20cerebrospinal%20fluid%20proteins%20in%20a%20presymptomatic%20primary%20glioma%20model&rft.jtitle=PloS%20one&rft.au=Whitin,%20John%20C&rft.date=2012-11-19&rft.volume=7&rft.issue=11&rft.spage=e49724&rft.pages=e49724-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0049724&rft_dat=%3Cgale_plos_%3EA477064904%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326742741&rft_id=info:pmid/23185417&rft_galeid=A477064904&rft_doaj_id=oai_doaj_org_article_ff36ab1df69541618698c47897395eeb&rfr_iscdi=true |