Comparison of three oral selenium compounds in cancer patients: Evaluation of differential pharmacodynamic effects in normal and malignant cells.

Show simple item record Evans, Stephen en Jacobson, Gregory M en Goodman, Hugh JB en Bird, Steve en Jameson, Michael en 2020-02-13T02:59:41Z en 2020-03 en
dc.identifier.issn 0946-672X en
dc.identifier.uri en
dc.description.abstract BACKGROUND:Selenium (Se) compounds have demonstrated therapeutic synergism in combination with anticancer treatments whilst reducing normal tissue toxicities in a range of experimental models. While reduction in some toxicities of chemotherapy and radiation has been confirmed in randomised clinical trials, they have not been powered to evaluate improved anticancer efficacy. A lack of data on the clinical potencies of the main nutritionally-relevant forms of Se and the relationship between their pharmacokinetic (PK) profiles and pharmacodynamic (PD) effects in cancer patients has hampered progress to date. The primary objective of this study was to determine the dose and form of Se that can be most safely and effectively used in clinical trials in combination with anti-cancer therapies. STUDY METHODS:In a phase I randomised double-blinded study, the PD profile of sodium selenite (SS), Se-methylselenocysteine (MSC) and seleno-l-methionine (SLM) were compared in two cohorts of 12 patients, one cohort with chronic lymphocytic leukaemia (CLL) and the other with solid malignancies. All 24 patients were randomised to receive 400 μg of elemental Se as either SS, MSC or SLM, taken orally daily for 8 weeks. PD parameters were assessed before, during and 4 weeks after Se compound exposure in plasma and peripheral blood mononuclear cells (PBMCs). RESULTS:No significant sustained changes were observed in plasma concentrations of vascular endothelial growth factor-α (VEGF-α), expression of proteins associated with endoplasmic reticulum stress (the unfolded protein response) or in intracellular total glutathione in PBMCs, in either disease cohort or when grouped by Se compound. CONCLUSIONS:At the 400 μg dose level no substantial changes in PD parameters were noted. Extrapolating from pre-clinical data, the dose examined in this cohort was too low to achieve the Se plasma concentration (≥ 5 μM) expected to elicit significant PD effects. Recruitment of a subsequent cohort at higher doses to exceed this PK threshold is planned. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title Comparison of three oral selenium compounds in cancer patients: Evaluation of differential pharmacodynamic effects in normal and malignant cells. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.jtemb.2019.126446 en
pubs.begin-page 126446 en
pubs.volume 58 en
dc.rights.holder Copyright: The author en
pubs.publication-status Accepted en
dc.rights.accessrights en
pubs.subtype Journal Article en
pubs.elements-id 790118 en Medical and Health Sciences en School of Medicine en Waikato Clinical school en
dc.identifier.eissn 1878-3252 en
pubs.record-created-at-source-date 2019-12-16 en
pubs.dimensions-id 31838377 en

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