{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:47:00Z","timestamp":1790729220815,"version":"4.1.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS102669"],"award-info":[{"award-number":["R01NS102669"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS117104"],"award-info":[{"award-number":["R01NS117104"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS118039"],"award-info":[{"award-number":["R01NS118039"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50CA221747"],"award-info":[{"award-number":["P50CA221747"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Infiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in\n                    <jats:italic>isocitrate dehydrogenase 1<\/jats:italic>\n                    (IDH1\n                    <jats:sup>mut<\/jats:sup>\n                    ) or, less commonly,\n                    <jats:italic>IDH2<\/jats:italic>\n                    (together called \u201cIDH\n                    <jats:sup>mut<\/jats:sup>\n                    \u201d). These mutations alter cellular biochemistry, and IDH\n                    <jats:sup>mut<\/jats:sup>\n                    gliomas are generally less aggressive than IDH wild-type (IDH\n                    <jats:sup>wt<\/jats:sup>\n                    ) gliomas. Some preclinical studies and clinical trials have suggested that various forms of a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, adherence to a strict KD is difficult, and not all studies have shown promising results. Furthermore, no study has yet addressed whether IDH\n                    <jats:sup>mut<\/jats:sup>\n                    gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of a unrestricted, cycling KD (weekly alternating between KD and standard diet) in preclinical models of IDH\n                    <jats:sup>wt<\/jats:sup>\n                    versus IDH\n                    <jats:sup>mut<\/jats:sup>\n                    gliomas.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , simulating KD by treatment with the ketone body \u03b2-hydroxybutyrate had no effect on the proliferation of patient-derived IDH\n                    <jats:sup>wt<\/jats:sup>\n                    or IDH\n                    <jats:sup>mut<\/jats:sup>\n                    glioma cells, either in low or normal glucose conditions. Likewise, an unrestricted, cycling KD had no effect on the\n                    <jats:italic>in vivo<\/jats:italic>\n                    growth of patient-derived IDH\n                    <jats:sup>wt<\/jats:sup>\n                    or IDH\n                    <jats:sup>mut<\/jats:sup>\n                    gliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, this KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDH\n                    <jats:sup>mut<\/jats:sup>\n                    or IDH\n                    <jats:sup>wt<\/jats:sup>\n                    glioma. These data suggest that neither IDH\n                    <jats:sup>wt<\/jats:sup>\n                    nor IDH\n                    <jats:sup>mut<\/jats:sup>\n                    gliomas are particularly responsive to an unrestricted, cycling form of KD.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0257725","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T13:23:43Z","timestamp":1644326623000},"page":"e0257725","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["The efficacy of an unrestricted cycling ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma"],"prefix":"10.1371","volume":"17","author":[{"given":"Rodrigo","family":"Javier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Drumm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"McCortney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jann N.","family":"Sarkaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-9992","authenticated-orcid":true,"given":"Craig","family":"Horbinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"issue":"suppl_5","key":"pone.0257725.ref001","doi-asserted-by":"crossref","first-page":"v1","DOI":"10.1093\/neuonc\/nox158","article-title":"CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010\u20132014","volume":"19","author":"QT Ostrom","year":"2017","journal-title":"Neuro Oncol"},{"issue":"10","key":"pone.0257725.ref002","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":"The New England journal of medicine"},{"key":"pone.0257725.ref003","first-page":"1078","article-title":"Methylation-dependent Tissue Factor suppression contributes to the reduced malignancy of IDH1 mutant gliomas","volume":"28","author":"D Unruh","year":"2018","journal-title":"Clin Cancer Res"},{"issue":"2","key":"pone.0257725.ref004","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/sj.bjc.6602321","article-title":"Years of life lost (YLL) from cancer is an important measure of population burden\u2014and should be considered when allocating research funds","volume":"92","author":"NG Burnet","year":"2005","journal-title":"Br J Cancer"},{"issue":"5","key":"pone.0257725.ref005","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"D Hanahan","year":"2011","journal-title":"Cell"},{"issue":"6","key":"pone.0257725.ref006","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1085\/jgp.8.6.519","article-title":"THE METABOLISM OF TUMORS IN THE BODY","volume":"8","author":"O Warburg","year":"1927","journal-title":"J Gen Physiol"},{"issue":"5","key":"pone.0257725.ref007","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00401-013-1106-9","article-title":"What do we know about IDH1\/2 mutations so far, and how do we use it?","volume":"125","author":"C. 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