Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group

Clark, Larry

doi:10.1001/jama.276.24.1957

Cited by 1,257 publications

(1,071 citation statements)

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“…Several prominent clinical trials however employing dietary antioxidants yielded disappointing anticancer results 42, 43, 44. Thus, current consensus is that rather than attempting to neutralize ROS, treatment strategies aimed at reducing ROS production might represent an effective alternative approach 45.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Nox4‐dependent ROS signaling attenuates prostate fibroblast activation and abrogates stromal‐mediated protumorigenic interactions

Sampson

Brunner

Weber

et al. 2018

Intl Journal of Cancer

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Carcinoma‐associated fibroblasts (CAFs) play a key onco‐supportive role during prostate cancer (PCa) development and progression. We previously reported that the reactive oxygen species (ROS)‐producing enzyme NADPH oxidase 4 (Nox4) is essential for TGFβ1‐mediated activation of primary prostate human fibroblasts to a CAF‐like phenotype. This study aimed to further investigate the functional relevance of prostatic Nox4 and determine whether pharmacological inhibition of stromal Nox4 abrogates paracrine‐mediated PCa‐relevant processes. RNA in situ hybridization revealed significantly elevated Nox4 mRNA levels predominantly in the peri‐tumoral stroma of clinical PCa with intense stromal Nox4 staining adjacent to tumor foci expressing abundant TGFβ protein levels. At pharmacologically relevant concentrations, the Nox1/Nox4 inhibitor GKT137831 attenuated ROS production, CAF‐associated marker expression and migration of TGFβ1‐activated but not nonactivated primary human prostate fibroblasts. Similar effects were obtained upon shRNA‐mediated silencing of Nox4 but not Nox1 indicating that GKT137831 primarily abrogates TGFβ1‐driven fibroblast activation via Nox4 inhibition. Moreover, inhibiting stromal Nox4 abrogated the enhanced proliferation and migration of PCa cell lines induced by TGFβ1‐activated prostate fibroblast conditioned media. These effects were not restricted to recombinant TGFβ1 as conditioned media from PCa cell lines endogenously secreting high TGFβ1 levels induced fibroblast activation in a stromal Nox4‐ and TGFβ receptor‐dependent manner. Importantly, GKT137831 also attenuated PCa cell‐driven fibroblast activation. Collectively, these findings suggest the TGFβ‐Nox4 signaling axis is a key interface to dysregulated reciprocal stromal–epithelial interactions in PCa pathophysiology and provide a strong rationale for further investigating the applicability of Nox4 inhibition as a stromal‐targeted approach to complement current PCa treatment modalities.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Nox4‐dependent ROS signaling attenuates prostate fibroblast activation and abrogates stromal‐mediated protumorigenic interactions

Sampson

Brunner

Weber

et al. 2018

Intl Journal of Cancer

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“…Trace element Se has been regarded as a breast cancer preventive factor (Kallistratos et al, 1989;Medina et al, 2001). However, in a large study a nonsignificant relationship between Se supplementation and increased breast cancer risk was shown (Clark et al, 1996). Se absorption is a complex, poorly understood process.…”

Section: Discussionmentioning

confidence: 99%

Selenium in serum and neoplastic tissue in breast cancer: correlation with CEA

et al. 2006

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Trace element selenium (Se) is regarded to be a breast cancer preventive factor involved in multiple protective pathways. In all, 80 women with breast cancer who underwent a radical mastectomy were enrolled in the study. Serum Se and carcinoembryonic antigen levels were measured using a fluorometric and IRMA assay, respectively. Se tissue concentration was determined by a tissue extracting fluorometric assay. For statistical analysis purposes t -test was used and P -values <0.001 were regarded as statistically significant. Serum Se was 42.5±7.5 μ g l −1 in breast cancer patients and 67.6±5.36 μ g l −1 in the age-matched control group of healthy individuals. Serum carcinoembryonic antigen in patients was 10±1.7 U ml −1 (normal <2.5 U ml −1 in nonsmokers/<3.5 U ml −1 in smokers). A statistically significant difference was found for both serum Se and CEA between two groups studied ( P <0.001). Neoplastic tissue Se concentration was 2660±210 mg g −1 tissue; its concentration in the adjacent non-neoplastic tissue was 680±110 mg g −1 tissue ( P <0.001). An inverse relationship between Se and CEA serum levels was found in the two groups studied ( r =−0.794). There was no correlation between serum/tissue Se concentration and stage of the disease. The decrease in serum Se concentration as well as its increased concentration in the neoplastic breast tissue is of great significance. These alterations may reflect part of the defence mechanisms against the carcinogenetic process.

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“…cancer (8) . A range of health conditions relating to Se intake are considered elsewhere (9) and are discussed later in the present paper.…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Symposium on ‘Geographical and geological influences on nutrition’ Factors controlling the distribution of selenium in the environment and their impact on health and nutrition

2009

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Se is essential to human and animal health but can be toxic in excess. An interest in its geochemistry has developed alongside a greater understanding of its function in a number of health conditions. Geology exerts a strong control on the Se status of the surface environment; low-Se rock-types (0·05–0·09 mg Se/kg) make up the majority of rocks occurring at the Earth's surface, which in turn account for the generally low levels of Se in most soils. However, there are exceptions such as associations with sulfide mineralisation and in some types of sedimentary rocks (e.g. black shales) in which contents of Se can be much higher. Baseline geochemical data now enable a comparison to be made between environmental and human Se status, although a direct link is only likely to be seen if the population is dependent on the local environment for sustenance. This situation is demonstrated with an example from the work of the British Geological Survey in the Se-deficiency belt of China. The recent fall in the daily dietary Se intake in the UK is discussed in the context of human Se status and declining use of North American wheat in bread making. Generally, US wheat has ten times more Se than UK wheat, attributed to the fact that soils from the wheat-growing belt of America are more enriched in Se to a similar order of magnitude. In agriculture effective biofortification of crops with Se-rich fertilisers must be demonstrably safe to the environment and monitored appropriately and baseline geochemical data will enable this process to be done with confidence.

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Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group

Cited by 1,257 publications

References 0 publications

Inhibition of Nox4‐dependent ROS signaling attenuates prostate fibroblast activation and abrogates stromal‐mediated protumorigenic interactions

Inhibition of Nox4‐dependent ROS signaling attenuates prostate fibroblast activation and abrogates stromal‐mediated protumorigenic interactions

Selenium in serum and neoplastic tissue in breast cancer: correlation with CEA

Symposium on ‘Geographical and geological influences on nutrition’ Factors controlling the distribution of selenium in the environment and their impact on health and nutrition

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