{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:31:30Z","timestamp":1790688690978,"version":"4.1.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T00:00:00Z","timestamp":1416528000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0112945","type":"journal-article","created":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T18:47:31Z","timestamp":1416595651000},"page":"e112945","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":121,"title":["Involvement of the Kynurenine Pathway in Human Glioma Pathophysiology"],"prefix":"10.1371","volume":"9","author":[{"given":"Seray","family":"Adams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerrie L.","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Bustamante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chai K.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri","family":"Sundaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nady","family":"Braidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Brew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles J.","family":"Guillemin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,11,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1158\/1055-9965.EPI-09-1077","article-title":"Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis","volume":"19","author":"P Sreekanthreddy","year":"2010","journal-title":"Cancer Epidemiology Biomarkers & Prevention"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1056\/NEJM200101113440207","article-title":"Medical progress: Brain tumors","volume":"344","author":"LM DeAngelis","year":"2001","journal-title":"New England Journal of Medicine"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"R Stupp","year":"2005","journal-title":"New England Journal of Medicine"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/cncr.11666","article-title":"Is the long-term survival of patients with intracranial glioblastoma multiforme overstated?","volume":"98","author":"RE McLendon","year":"2003","journal-title":"Cancer"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.bbapap.2010.12.003","article-title":"Structure, mechanism, and substrate specificity of kynureninase","volume":"1814","author":"RS Phillips","year":"2011","journal-title":"Biochimica Et Biophysica Acta-Proteins and Proteomics"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1111\/j.1742-4658.2012.08485.x","article-title":"Quinolinic acid, the inescapable neurotoxin","volume":"279","author":"GJ Guillemin","year":"2012","journal-title":"Febs Journal"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0014-2999(02)01851-4","article-title":"The pharmacological manipulation of glutamate receptors and neuroprotection","volume":"447","author":"TW Stone","year":"2002","journal-title":"European Journal of Pharmacology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/neu.10146","article-title":"Unconventional ligands and modulators of nicotinic receptors","volume":"53","author":"EF Pereira","year":"2002","journal-title":"J Neurobiol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.bbrc.2007.10.197","article-title":"GPR35 is a functional receptor in rat dorsal root ganglion neurons","volume":"365","author":"H Ohshiro","year":"2008","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.ntt.2011.07.002","article-title":"On the antioxidant properties of kynurenic acid: Free radical scavenging activity and inhibition of oxidative stress","volume":"33","author":"R Lugo-Huitron","year":"2011","journal-title":"Neurotoxicology and Teratology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.gene.2007.04.010","article-title":"Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice","volume":"396","author":"HJ Ball","year":"2007","journal-title":"Gene"},{"key":"ref12","first-page":"2863","article-title":"Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment","volume":"50","author":"G Werner-Felmayer","year":"1990","journal-title":"Cancer Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1084\/jem.189.9.1363","article-title":"Inhibition of T cell proliferation by macrophage tryptophan catabolism","volume":"189","author":"DH Munn","year":"1999","journal-title":"Journal of Experimental Medicine"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1073\/pnas.1113873109","article-title":"Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase","volume":"109","author":"L Pilotte","year":"2012","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/nm934","article-title":"Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase","volume":"9","author":"C Uyttenhove","year":"2003","journal-title":"Nat Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1158\/1078-0432.CCR-05-1966","article-title":"Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells","volume":"12","author":"G Brandacher","year":"2006","journal-title":"Clin Cancer Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.4161\/cbt.6.8.4446","article-title":"Indoleamine 2,3-dioxygenose (IDO) expression in lung cancer","volume":"6","author":"V Karanikas","year":"2007","journal-title":"Cancer Biology & Therapy"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"6030","DOI":"10.1158\/1078-0432.CCR-04-2671","article-title":"Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells","volume":"11","author":"A Okamoto","year":"2005","journal-title":"Clinical Cancer Research"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1007\/s10585-009-9290-7","article-title":"Prognostic value of indoleamine 2,3-dioxygenase expression in high grade osteosarcoma","volume":"26","author":"H Urakawa","year":"2009","journal-title":"Clinical & Experimental Metastasis"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3171\/2008.10.JNS081141","article-title":"Indoleamine 2,3-dioxygenase as a new target for malignant glioma therapy Laboratory investigation","volume":"111","author":"T Miyazaki","year":"2009","journal-title":"Journal of Neurosurgery"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/0167-4889(89)90087-6","article-title":"Characteristics of interferon induced tryptophan metabolism in human cells in vitro","volume":"1012","author":"G Werner-Felmayer","year":"1989","journal-title":"Biochim Biophys Acta"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1002\/eji.200939535","article-title":"Antimicrobial and immunoregulatory properties of human tryptophan 2,3-dioxygenase","volume":"39","author":"SK Schmidt","year":"2009","journal-title":"European Journal of Immunology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature10491","article-title":"An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor","volume":"478","author":"CA Opitz","year":"2011","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"6110","DOI":"10.1158\/1078-0432.CCR-12-2130","article-title":"IDO Expression in Brain Tumors Increases the Recruitment of Regulatory T Cells and Negatively Impacts Survival","volume":"18","author":"DA Wainwright","year":"2012","journal-title":"Clinical Cancer Research"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1126\/scitranslmed.3000632","article-title":"Tryptophan Catabolism by Indoleamine 2,3-Dioxygenase 1 Alters the Balance of T(H)17 to Regulatory T Cells in HIV Disease","volume":"2","author":"D Favre","year":"2010","journal-title":"Science Translational Medicine"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.4049\/jimmunol.176.11.6752","article-title":"The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells","volume":"176","author":"F Fallarino","year":"2006","journal-title":"J Immunol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jneumeth.2007.07.005","article-title":"Cellular composition of human glial cultures from adult biopsy brain tissue","volume":"166","author":"HA Gibbons","year":"2007","journal-title":"Journal of Neuroscience Methods"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/sj.jcbfm.9600199","article-title":"In vivo uptake and metabolism of alpha-[C-11] methyl-L-tryptophan in human brain tumors","volume":"26","author":"C Juhasz","year":"2006","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1179\/135100000101535357","article-title":"IDO induction in IFN-gamma activated astroglia: a role in improving cell viability during oxidative stress","volume":"5","author":"RS Grant","year":"2000","journal-title":"Redox Rep"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"12884","DOI":"10.1523\/JNEUROSCI.4101-07.2007","article-title":"Characterization of the Kynurenine Pathway in Human Neurons","volume":"27","author":"GJ Guillemin","year":"2007","journal-title":"J Neurosci"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1128\/CVI.05402-11","article-title":"Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis","volume":"19","author":"Y Suzuki","year":"2012","journal-title":"Clinical and Vaccine Immunology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1158\/1078-0432.CCR-05-1966","article-title":"Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: Effect on tumor-infiltrating T cells","volume":"12","author":"G Brandacher","year":"2006","journal-title":"Clinical Cancer Research"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1084\/jem.189.9.1363","article-title":"Inhibition of T cell proliferation by macrophage tryptophan catabolism","volume":"189","author":"DH Munn","year":"1999","journal-title":"J Exp Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11010-007-9635-y","article-title":"Differential immunosuppressive effect of indoleamine 2,3-dioxygenase (IDO) on primary human CD4(+) and CD8 (+) T cells","volume":"309","author":"F Forouzandeh","year":"2008","journal-title":"Mol Cell Biochem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1084\/jem.20020121","article-title":"Tryptophan-derived Catabolites Are Responsible for Inhibition of T and Natural Killer Cell Proliferation Induced by Indoleamine 2,3-Dioxygenase","volume":"196","author":"G Frumento","year":"2002","journal-title":"J Exp Med"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.gene.2005.09.034","article-title":"Characterization of kynurenine aminotransferase III, a novel member of a phylogenetically conserved KAT family","volume":"365","author":"P Yu","year":"2006","journal-title":"Gene"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1471-4159.2007.04556.x","article-title":"Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain","volume":"102","author":"P Guidetti","year":"2007","journal-title":"J Neurochem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1046\/j.1471-4159.2001.00498.x","article-title":"Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection","volume":"78","author":"GJ Guillemin","year":"2001","journal-title":"Journal of Neurochemistry"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s11064-005-6178-z","article-title":"Demonstration of Kynurenine Aminotransferases I and II and Characterization of Kynurenic Acid Synthesis in Oligodendrocyte Cell Line (OLN-93)","volume":"30","author":"K Wejksza","year":"2005","journal-title":"Neurochem Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/(SICI)1097-4547(19971101)50:3<457::AID-JNR12>3.0.CO;2-3","article-title":"Characterization of rat brain kynurenine aminotransferases I and II","volume":"50","author":"P Guidetti","year":"1997","journal-title":"J Neurosci Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/j.1440-1819.2008.01854.x","article-title":"Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-alpha: Course and relationship with psychiatric status","volume":"62","author":"AR Van Gool","year":"2008","journal-title":"Psychiatry and Clinical Neurosciences"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.bbi.2011.05.005","article-title":"Reversal of imbalance between kynurenic acid and 3-hydroxykynurenine by antipsychotics in medication-naive and medication-free schizophrenic patients","volume":"25","author":"AM Myint","year":"2011","journal-title":"Brain Behavior and Immunity"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jad.2006.07.013","article-title":"Kynurenine pathway in major depression: Evidence of impaired neuroprotection","volume":"98","author":"AM Myint","year":"2007","journal-title":"Journal of Affective Disorders"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0021-9258(18)71231-3","article-title":"STUDIES OF THE ENZYMATIC TRANSFORMATION OF 3-HYDROXYANTHRANILATE TO QUINOLINATE","volume":"211","author":"CL Long","year":"1954","journal-title":"Journal of Biological Chemistry"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1111\/j.1471-4159.2009.05868.x","article-title":"Age and circadian influences on picolinic acid concentrations in human cerebrospinal fluid","volume":"108","author":"SE Coggan","year":"2009","journal-title":"Journal of Neurochemistry"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"10412","DOI":"10.1021\/bi060903q","article-title":"Crystal structure of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase: insight into the active site and catalytic mechanism of a novel decarboxylation reaction","volume":"45","author":"D Martynowski","year":"2006","journal-title":"Biochemistry"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Ikeda M, Tsuji H, Nakamura S, Ichiyama A, Nishizuk. Y. <etal>et al<\/etal>. Studies on biosynthesis of nicotinamide adenine dinucleotide.2. a role of picolinic carboxylase in biosynthesis of nicotinamide adenine dinucleotide from tryptophan in mammals. Journal of Biological Chemistry. 1965;240:1395\u2013&amp;.","DOI":"10.1016\/S0021-9258(18)97589-7"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/j.1742-4658.2007.05635.x","article-title":"Tissue expression and biochemical characterization of human 2-amino 3-carboxymuconate 6-semialdehyde decarboxylase, a key enzyme in tryptophan catabolism","volume":"274","author":"L Pucci","year":"2007","journal-title":"Febs J"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.2741\/2194","article-title":"NAD+ and NADH in brain functions, brain diseases and brain aging","volume":"12","author":"W Ying","year":"2007","journal-title":"Front Biosci"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1111\/j.1742-4658.2011.08366.x","article-title":"Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats","volume":"278","author":"N Braidy","year":"2011","journal-title":"Febs Journal"},{"key":"ref51","first-page":"6524","article-title":"The Kynurenine Pathway in Brain Tumor Pathogenesis (vol 72, pg 5649, 2012)","volume":"72","author":"S Adams","year":"2012","journal-title":"Cancer Research"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1158\/0008-5472.CAN-12-3831","article-title":"The endogenous tryptophan metabolite and NAD+ precursor quinolinic acid confers resistance of gliomas to oxidative stress","volume":"73","author":"F Sahm","year":"2013","journal-title":"Cancer Res"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrn3257","article-title":"Kynurenines in the mammalian brain: when physiology meets pathology","volume":"13","author":"R Schwarcz","year":"2012","journal-title":"Nat Rev Neurosci"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Locasale JW, Melman T, Song SS, Yang XM, Swanson KD, <etal>et al<\/etal>. Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma. Molecular &amp; Cellular Proteomics. 2012.11.","DOI":"10.1074\/mcp.M111.014688"},{"key":"ref55","first-page":"1327","article-title":"Diagnostic markers for glioblastoma","volume":"26","author":"CS Jung","year":"2011","journal-title":"Histology and Histopathology"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"e19823","DOI":"10.1371\/journal.pone.0019823","article-title":"The indoleamine-2,3-dioxygenase (IDO) inhibitor 1-methyl-D-tryptophan upregulates IDO1 in human cancer cells","volume":"6","author":"CA Opitz","year":"2011","journal-title":"Plos One"},{"key":"ref57","unstructured":"Gomez GG, Kruse CA. Isolation and Culture of Human Brain Tumor Cells. 2003; Cancer Cell Culture: Methods and Protocols."},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"Smythe GA, Poljak A, Bustamante S, Braga O, Maxwell A, <etal>et al<\/etal>. ECNI GC-MS analysis of picolinic and quinolinic acids and their amides in human plasma, CSF, and brain tissue. In: Allegri G, Costa CVL, Ragazzi E, Steinhart H, Varesio L, editors.Developments in Tryptophan and Serotonin Metabolism.New York: Kluwer Academic\/Plenum Publ. 2003. pp.705\u2013712.","DOI":"10.1007\/978-1-4615-0135-0_83"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1111\/j.1440-1681.1994.tb02460.x","article-title":"Kynurenic acid, an endogenous glutamate antagonist, in SHR and WKY rats: possible role in central blood pressure regulation","volume":"21","author":"V Kapoor","year":"1994","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"5649","DOI":"10.1158\/0008-5472.CAN-12-0549","article-title":"The kynurenine pathway in brain tumor pathogenesis","volume":"72","author":"S Adams","year":"2012","journal-title":"Cancer Res"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0112945","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T03:07:17Z","timestamp":1650683237000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0112945"}},"subtitle":[],"editor":[{"given":"Adriano","family":"Boasso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,11,21]]},"references-count":60,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,11,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0112945","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,21]]}}}