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Sodium homeostasis in the tumour microenvironment.
Leslie, TK, James, AD, Zaccagna, F, Grist, JT, Deen, S, Kennerley, A, Riemer, F, Kaggie, JD, Gallagher, FA, Gilbert, FJ, et al
Biochimica et biophysica acta. Reviews on cancer. 2019;(2):188304
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Abstract
The concentration of sodium ions (Na+) is raised in solid tumours and can be measured at the cellular, tissue and patient levels. At the cellular level, the Na+ gradient across the membrane powers the transport of H+ ions and essential nutrients for normal activity. The maintenance of the Na+ gradient requires a large proportion of the cell's ATP. Na+ is a major contributor to the osmolarity of the tumour microenvironment, which affects cell volume and metabolism as well as immune function. Here, we review evidence indicating that Na+ handling is altered in tumours, explore our current understanding of the mechanisms that may underlie these alterations and consider the potential consequences for cancer progression. Dysregulated Na+ balance in tumours may open opportunities for new imaging biomarkers and re-purposing of drugs for treatment.
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Effects of Sodium Restriction on Activation of the Renin-Angiotensin-Aldosterone System and Immune Indices During HIV Infection.
Srinivasa, S, Burdo, TH, Williams, KC, Mitten, EK, Wong, K, Fitch, KV, Stanley, T, Adler, GK, Grinspoon, SK
The Journal of infectious diseases. 2016;(9):1336-1340
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Abstract
BACKGROUND Human immunodeficiency virus (HIV)-infected patients demonstrate increased activation of the renin-angiotensin-aldosterone system (RAAS). We evaluated changes in immune markers with physiological RAAS activation. METHODS Immune activation markers were assessed serially in 18 HIV-infected and 7 non-HIV-infected subjects consuming an ad libitum diet followed by a standardized low-sodium diet. RESULTS Levels of CCL-2 (P = .0004) and soluble CD163 (P = .0001) significantly increased with sodium restriction and RAAS activation, compared with levels in individuals with ad libitum sodium intake, among chronically treated HIV-infected subjects (mean duration of ART [±SEM], 11 ± 1 years), but not among non-HIV-infected subjects of similar age and sex. CONCLUSIONS Dietary sodium restriction, which activates RAAS, uniquely stimulates critical indices of immune activation during HIV infection. CLINICAL TRIALS REGISTRATION NCT01407237.