dc.contributor.author |
Evans, Stephen |
en |
dc.contributor.author |
Jacobson, Gregory M |
en |
dc.contributor.author |
Goodman, Hugh JB |
en |
dc.contributor.author |
Bird, Steve |
en |
dc.contributor.author |
Jameson, Michael |
en |
dc.date.accessioned |
2020-02-13T02:59:41Z |
en |
dc.date.issued |
2020-03 |
en |
dc.identifier.issn |
0946-672X |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/49959 |
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 |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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 |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
790118 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
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 |