Proposed Supplemental Dosages of Selenium for a Phase I Trial Based on Dietary and Supplemental Selenium Intakes and Episodes of Chronic Selenosis

Chen, J.; Clark, Larry

doi:10.3109/10915818609140737

Cited by 19 publications

(5 citation statements)

References 6 publications

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“…1985;Rylander, 1990;and Lange, 1991). Future studies are needed to evaluate selenium as a anti-cancer therapy agent (Chen and Clark, 1986) and for cancer prevention (Lange, et. al.…”

Section: Discussionmentioning

confidence: 96%

Reanalysis of Epidemiological Data for Selenium Anti-Cancer Activity

Lange

1991

Toxicol Ind Health

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Investigations of the health effects of selenium have repeatedly noted an inverse relationship of selenium (both soil and human sera) and decreased prevalence of cancer. This has been found in cross sectional, case-control and ecological study designs. Reanalysis of age-adjusted death rates by cancer site revealed a significant inverse relationship for lung and all cancer with blood selenium. Methodological problems in this type of research is discussed.

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“…1985;Rylander, 1990;and Lange, 1991). Future studies are needed to evaluate selenium as a anti-cancer therapy agent (Chen and Clark, 1986) and for cancer prevention (Lange, et. al.…”

Section: Discussionmentioning

confidence: 96%

Reanalysis of Epidemiological Data for Selenium Anti-Cancer Activity

Lange

1991

Toxicol Ind Health

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“…22 For cancer chemoprevention, a dose of 750-4,990 g/day has been suggested. 5 Consumption of 150 g of the liver of pig 7 would have provided 495 g of selenium.…”

Section: Discussionmentioning

confidence: 99%

Selenium Elimination in Pigs after an Outbreak of Selenium Toxicosis

et al. 1999

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Abstract. In May 1996, 150 grower pigs in 5 California counties were exposed to selenium-contaminated feed distributed by a single feed company. Feed samples from 20 herds had a mean selenium concentration of 121.7 ppm dry weight (range, 22.1-531 ppm). In San Luis Obispo County, 52 pigs in 24 herds were exposed to the feed, and 8 pigs died with signs of paralysis. Bilateral symmetrical poliomyelomalacia involving the ventral horns of the cervical and lumbar intumescence was evident on histologic examination of spinal cord from affected pigs. Of 44 surviving exposed pigs, 33 (75%) exhibited signs of selenosis, including anorexia, alopecia, and hoof lesions. Thirty-nine of 44 pigs (88.6%) had elevated (Ͼ1 ppm) blood selenium concentrations. Surviving exposed pigs were changed to a standard commercial ration containing approximately 0.5 ppm (dry weight) selenium. Blood selenium concentrations were determined weekly for 46 days following removal of the contaminated feed and were compared with values of 20 control pigs fed a standard commercial ration. Mean (ϮSD) blood selenium concentrations of exposed pigs were 3.2 Ϯ 2.6 ppm at the initial sampling and 0.4 Ϯ 0.1 ppm after 46 days. Mean blood selenium concentrations of Յ 0.3 ppm for control pigs at all samplings were significantly lower (P Ͻ 0.001) than concentrations for exposed pigs. Muscle and liver samples of 22 of the 44 exposed pigs were collected at slaughter approximately 72 days after withdrawal of the selenium-contaminated feed. Muscle samples had a mean selenium concentration of 0.36 ppm (wet weight). Liver samples had a mean selenium concentration of 1.26 ppm (wet weight). One liver sample had a selenium value in the toxic range for pigs (3.3 ppm wet weight; reference range, 0.4-1.2 ppm). A 1-compartment pharmacokinetic model of selenium elimination in exposed pigs was generated, and the geometric mean blood selenium elimination half-life was estimated to be 12 days. The 60-day withdrawal time recommended by the Food Animal Residue Avoidance Database was considered sufficient to allow safe human consumption of tissues from exposed pigs.Selenium is an essential trace element for swine, necessary for cells to detoxify peroxides. 29 It is one of the most toxic trace elements 26,33 and has a narrow margin of safety. Toxicosis has been reported in swine after repeated ingestion of feed containing Ͼ5 ppm selenium (dry weight). 4,12,[24][25][26] Signs of selenium toxicosis in swine include anorexia, alopecia, separation of hoof and skin at the coronary band, degenerative changes in the liver and kidney, and poliomyelomalacia. 16,26,27,33 In 1974, the US Food and Drug Administration (FDA) authorized the addition of a sodium salt of selenium to swine feed at a concentration of 0.1 ppm (dry weight) in the complete ration. 32 Current FDA regulations allow a maximum of 0.3 ppm (dry weight) in the complete ration as either inorganic sodium selenite or selenate. 7 Sodium selenite is the most commonly used selenium compound in domestic feed because of its lower cost, a...

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“…A number of clinical prevention trials have utilized SLM, sodium selenite, and selenized yeast [ 34 , 37 , 38 ]. Table 1 summarizes the different forms of Se that have been evaluated in in vitro and in vivo models.…”

Section: Introductionmentioning

confidence: 99%

Selenium targets resistance biomarkers enhancing efficacy while reducing toxicity of anti-cancer drugs: preclinical and clinical development

2018

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Selenium (Se)-containing molecules exert antioxidant properties and modulate targets associated with tumor growth, metastasis, angiogenesis, and drug resistance. Prevention clinical trials with low-dose supplementation of different types of Se molecules have yielded conflicting results. Utilizing several xenograft models, we earlier reported that the enhanced antitumor activity of various chemotherapeutic agents by selenomethione and Se-methylselenocysteine in several human tumor xenografts is highly dose- and schedule-dependent. Further, Se pretreament offered selective protection of normal tissues from drug-induced toxicity, thereby allowing higher dosing than maximum tolerated doses.These enhanced therapeutic effects were associated with inhibition of hypoxia-inducible factor 1- and 2-alpha (HIF1α, HIF2α) protein, nuclear factor (erythyroid-derived 2)-like 2 (Nrf2) and pair-related homeobox-1 (Prx1) transcription factors, downregulation of oncogenic- and upregulation of tumor suppressor miRNAs. This review provides: 1) a brief update of clinical prevention trials with Se; 2) advances in the use of specific types, doses, and schedules of Se that selectively modulate antitumor activity and toxicity of anti-cancer drugs; 3) identification of targets selectively modulated by Se; 4) plasma and tumor tissue Se levels achieved after oral administration of Se in xenograft models and cancer patients; 5) development of a phase 1 clinical trial with escalating doses of orally administered selenomethionine in sequential combination with axitinib to patients with advanced clear cell renal cell carcinoma; and 6) clinical prospects for future therapeutic use of Se in combination with anticancer drugs.

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Proposed Supplemental Dosages of Selenium for a Phase I Trial Based on Dietary and Supplemental Selenium Intakes and Episodes of Chronic Selenosis

Cited by 19 publications

References 6 publications

Reanalysis of Epidemiological Data for Selenium Anti-Cancer Activity

Reanalysis of Epidemiological Data for Selenium Anti-Cancer Activity

Selenium Elimination in Pigs after an Outbreak of Selenium Toxicosis

Selenium targets resistance biomarkers enhancing efficacy while reducing toxicity of anti-cancer drugs: preclinical and clinical development

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