{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:01:35Z","timestamp":1792004495550,"version":"4.4.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072950"],"award-info":[{"award-number":["82072950"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M702908"],"award-info":[{"award-number":["2021M702908"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Province Postdoctoral Research Excellence Funding Project","award":["ZJ2021039"],"award-info":[{"award-number":["ZJ2021039"]}]},{"name":"Zhejiang Provincial Health Commission","award":["2024037191"],"award-info":[{"award-number":["2024037191"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC; RAIR-DTC) have a poor prognosis. The aim of this study was to provide new insights and possibilities for the diagnosis and treatment of RAIR-DTC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The metabolomics of 24 RAIR-DTC and 18 non-radioiodine-refractory (NonRAIR) DTC patients samples were analyzed by liquid chromatograph-mass spectrometry. Cellular radioiodine uptake was detected with \u03b3 counter. Sodium iodide symporter (NIS) expression and thyroid stimulating hormone receptor (TSHR) were measured by Western blot analysis. CCK8 and colony formation assays were used to measure cellular proliferation. Scratch and transwell assays were performed to assess cell migration and invasion. Annexin V\/PI staining was used to detect cell apoptosis. Cell growth in vivo was evaluated by a tumor xenograft model. The acetoacetate (AcAc) level was measured by ELISA. Pathological changes, Ki67, NIS, and TSHR expression were investigated by immunohistochemistry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The metabolite profiles of RAIR could be distinguished from those of NonRAIR, with AcAc significantly lower in RAIR. The significantly different metabolic pathway was ketone body metabolism. AcAc increased NIS and TSHR expression and improved radioiodine uptake. AcAc inhibited cell proliferation, migration, and invasion, and as well promoted cell apoptosis. Ketogenic diet (KD) elevated AcAc levels and significantly suppressed tumor growth, as well as improved NIS and TSHR expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Significant metabolic differences were observed between RAIR and NonRAIR, and ketone body metabolism might play an important role in RAIR-DTC. AcAc improved cellular iodine uptake and had antitumor effects for thyroid carcinoma. KD might be a new therapeutic strategy for RAIR-DTC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae075","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T07:44:03Z","timestamp":1716018243000},"page":"e1120-e1131","source":"Crossref","is-referenced-by-count":10,"title":["Metabolomics reveals the implication of acetoacetate and ketogenic diet therapy in radioiodine-refractory differentiated thyroid carcinoma"],"prefix":"10.1093","volume":"29","author":[{"given":"Jiaqi","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Head and Neck Cancer Translation Research of Zhejiang Province, Zhejiang Cancer Hospital , Hangzhou, People\u2019s Republic of China"},{"name":"Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital) , Hangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Head and Neck Cancer Translation Research of Zhejiang Province, Zhejiang Cancer Hospital , Hangzhou, People\u2019s Republic of China"},{"name":"Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital) , Hangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Xuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Head and Neck Cancer Translation Research of Zhejiang Province, Zhejiang Cancer Hospital , Hangzhou, People\u2019s Republic of China"},{"name":"Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital) , Hangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Mao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Head and Neck Cancer Translation Research of Zhejiang Province, Zhejiang Cancer Hospital , Hangzhou, People\u2019s Republic of China"},{"name":"Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital) , Hangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Head and Neck Cancer Translation Research of Zhejiang Province, Zhejiang Cancer Hospital , Hangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Head and Neck Cancer Translation Research of Zhejiang Province, Zhejiang Cancer Hospital , Hangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahuan","family":"Song","sequence":"additional","affiliation":[{"name":"Cancer Center, Department of Nuclear Medicine, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College , Hangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5337-4661","authenticated-orcid":false,"given":"Xin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Head and Neck Cancer Translation Research of Zhejiang Province, Zhejiang Cancer Hospital , Hangzhou, People\u2019s Republic of China"},{"name":"Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital) , Hangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,18]]},"reference":[{"key":"2024090704220424100_CIT0001","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 cancers in 185 countries","volume-title":"CA Cancer J Clin","author":"Sung","year":"2021"},{"key":"2024090704220424100_CIT0002","first-page":"5448","article-title":"Radioiodine refractoriness score: a multivariable prediction model for postoperative radioiodine-refractory differentiated thyroid carcinomas","volume-title":"Cancer Med","author":"Li","year":"2018"},{"key":"2024090704220424100_CIT0003","first-page":"1109439","article-title":"A user-friendly nomogram for predicting radioiodine refractory differentiated thyroid cancer","volume-title":"Front Endocrinol","author":"Meng","year":"2023"},{"key":"2024090704220424100_CIT0004","first-page":"1594","article-title":"Multi-organ distant metastases confer worse disease-specific survival in differentiated thyroid cancer","volume-title":"Thyroid","author":"Wang","year":"2014"},{"key":"2024090704220424100_CIT0005","first-page":"812","article-title":"The medical treatment of radioiodine-refractory differentiated thyroid cancers in 2019. 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