{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:29:46Z","timestamp":1785421786704,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001529","name":"Waikato Medical Research Foundation","doi-asserted-by":"publisher","award":["310"],"award-info":[{"award-number":["310"]}],"id":[{"id":"10.13039\/501100001529","id-type":"DOI","asserted-by":"publisher"}]},{"award":["310"],"award-info":[{"award-number":["310"]}],"id":[{"id":"https:\/\/ror.org\/001xe7y71","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001552","name":"Genesis Oncology Trust","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001552","id-type":"DOI","asserted-by":"publisher"}]},{"award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/03960jw18","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Cycle for Life","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>High-dose selenium (Se) as selenomethionine (SLM) and sodium selenite (SS) can improve the efficacy of cancer therapies while reducing toxicity. Se-methylselenocysteine (MSC) is effective in preclinical models but has not been evaluated in cancer trials. This phase Ib randomised, double-blinded trial explored the safety, pharmacokinetics (PK) and selected pharmacodynamic (PD) mechanisms of MSC, SLM and SS to guide future trials. Nine participants with metastatic cancer took Se 1600 \u03bcg\/day for 4 weeks, then 6400 \u03bcg\/day for 4 weeks, as MSC, SLM, or SS, with safety, PK, and PD assessments at baseline then every 4 weeks for 12 weeks. No dose-limiting toxicities occurred, and all adverse events were grades 1\u20132, mainly gastrointestinal. Total plasma Se increased after 8 weeks to mean 27.2 \u03bcM with SLM, 4.14 \u03bcM with MSC and 3.90 \u03bcM with SS. No significant changes in DNA damage or intracellular glutathione were observed in peripheral blood mononuclear cells. Mean plasma selenoprotein P (SEPP) increased from 3.74 mg\/L at baseline to 4.66 mg\/L and 5.13 mg\/L after 4 and 8 weeks (p = 0.136 and 0.104, respectively). More detailed evaluations of safety, PK and PD mechanisms are needed to determine a recommended Se compound and dose for larger trials in combination with cancer therapies.<\/jats:p>","DOI":"10.3390\/ijms27156618","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"6618","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploration of Safety, Pharmacokinetics and Selected Pharmacodynamic Mechanisms of High-Dose Se-Methylselenocysteine, L-Selenomethionine and Selenite in a Phase Ib Trial in Cancer Patients"],"prefix":"10.3390","volume":"27","author":[{"given":"Catherine M.","family":"Turnbull","sequence":"first","affiliation":[{"name":"Faculty of Medical and Health Sciences, Waikato Clinical Campus, University of Auckland, Hamilton 3204, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3426-0973","authenticated-orcid":false,"given":"Stephen O.","family":"Evans","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences, University of Waikato, Hamilton 3240, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-4293","authenticated-orcid":false,"given":"Linda M.","family":"Peters","sequence":"additional","affiliation":[{"name":"School of Science, University of Waikato, Hamilton 3240, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee J.","family":"Goodall","sequence":"additional","affiliation":[{"name":"School of Science, University of Waikato, Hamilton 3240, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig K.","family":"Burns","sequence":"additional","affiliation":[{"name":"School of Science, University of Waikato, Hamilton 3240, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh J. B.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Haematology Department, Waikato Hospital, Hamilton 3204, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Briggs","sequence":"additional","affiliation":[{"name":"Oncology Department, Waikato Hospital, Hamilton 3204, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7068-4311","authenticated-orcid":false,"given":"Michael B.","family":"Jameson","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Waikato Clinical Campus, University of Auckland, Hamilton 3204, New Zealand"},{"name":"Oncology Department, Waikato Hospital, Hamilton 3204, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/S0140-6736(11)61452-9","article-title":"Selenium and human health","volume":"379","author":"Rayman","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1079\/PNS2005467","article-title":"Selenium in cancer prevention: A review of the evidence and mechanism of action","volume":"64","author":"Rayman","year":"2005","journal-title":"Proc. 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