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Distant metastases form monophyletic groups and have reduced clonality compared to LN metastases, suggesting different evolutionary mechanisms between LN metastases and distant metastases (154)

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The potential underlying mechanism involves disruption of intracellular functions, such as excessive ROS accumulation, endoplasmic dysfunction, and mitochondrial dysfunction

The frequent systemic side effects associated with the use of systemic CAIs may adversely affect compliance

J Pharmacol Exp Ther 333: 939947, 2010 [DOI] [PMC free article] [PubMed] [Google Scholar] 58.Mannucci L, Pastore A, Rizzo C, Piemonte F, Rizzoni G, Emma F: Impaired activity of the gamma-glutamyl cycle in nephropathic cystinosis fibroblasts

For example, reports of enzyme inhibition or modulation of signalling by silymarin derivatives in in vitro systems might partly reflect nonspecific adsorption or redox interference, rather than a real biochemical effect