Abstract

Experiments carried out on different tumor cell lines showed a significative growth reduction of all treated lines due to the administration of zebrafish embryo extracts withdrawn at different stem cells differentiation stages. Research conducted in order to establish which molecular events were involved in control and downregulation of cancer cell lines demonstrated a transcriptional regulation of the key cell cycle onco-supressor gene, like p53 and a post-translational modification of molecules, like pRb. Research on apoptosis and differentiation processes showed that stem cells differentiating factors (SCDF) induce caspase-3 activation, mainly through E2F-1 gene regulation, thus hyper expressing c-Myc and activating a p73-dependent apoptotic pathway. Moreover, we demonstrated a concurrent and significative normalization of the e-cadherin/β-catenin expression, with an e-cadherin rise. Administration of SCDF in an open clinical randomized clinical trail (RCT) conducted on 179 patients affected by intermediate–advanced hepatocellular carcinoma (HCC) resulted in 19.8% patients with disease regression (whom 2.6% with a complete regressions), 16% patients with stable disease and a significative increase in median overall survival. A subsequent analysis of 50 intermediate–advanced HCC patients showed 13.1% complete regressions. SCDF showed also to significantly prevent neurodegenerative processes induced by strong doses of N-methyl-D-aspartate in the rat hippocampus cell line. Finally, clinical application of topic SCDF on psoriasis patients resulted in almost 80% reduction or remission of the disease. The use of SCDF leads us to conceive a new body–mind complex adaptive system model that integrates concepts like epigenetic and information transmission in biological systems and the psyconeuroendocrinology system.

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