Treatment with the vascular disruptive agent OXi4503 induces an immediate and widespread epithelial to mesenchymal transition in the surviving tumor

Epithelial to mesenchymal transition (EMT) is considered an important mechanism in tumor resistance to drug treatments; however, in vivo observation of this process has been limited. In this study we demonstrated an immediate and widespread EMT involving all surviving tumor cells following treatment of a mouse model of colorectal liver metastases with the vascular disruptive agent OXi4503. EMT was characterized by significant downregulation of E-cadherin, relocation and nuclear accumulation of b-catenin as well as significant upregulation of ZEB1 and vimentin. Concomitantly, significant temporal upregulation in hypoxia and the pro-angiogenic growth factors hypoxia-inducible factor 1-alpha, hepatocyte growth factor, vascular endothelial growth factor and transforming growth factor-beta were seen within the surviving tumor. The process of EMT was transient and by 5 days after treatment tumor cell reversion to epithelial morphology was evident. This reversal, termed mesenchymal to epithelial transition (MET) is a process implicated in the development of new metastases but has not been observed in vivo histologically. Similar EMT changes were observed in response to other antitumor treatments including chemotherapy, thermal ablation, and antiangiogenic treatments in our mouse colorectal metastasis model and in a murine orthotopic breast cancer model after OXi4503 treatment. These results suggest that EMT may be an early mechanism adopted by tumors in response to injury and hypoxic stress, such that inhibition of EMT in combination with other therapies could play a significant role in future cancer therapy.

Lyprinol : is it a useful anti-inflammatory agent?

The New Zealand green lipped mussel preparation Lyprinol is available without a prescription from a supermarket, pharmacy or Web. The Food and Drug Administration have recently warned Lyprinol USA about their extravagant anti-inflammatory claims for Lyprinol appearing on the web. These claims are put to thorough review. Lyprinol does have anti-inflammatory mechanisms, and has anti-inflammatory effects in some animal models of inflammation. Lyprinol may have benefits in dogs with arthritis. There are design problems with the clinical trials of Lyprinol in humans as an anti-inflammatory agent in osteoarthritis and rheumatoid arthritis, making it difficult to give a definite answer to how effective Lyprinol is in these conditions, but any benefit is small. Lyprinol also has a small benefit in atopic allergy. As anti-inflammatory agents, there is little to choose between Lyprinol and fish oil. No adverse effects have been reported with Lyprinol. Thus, although it is difficult to conclude whether Lyprinol does much good, it can be concluded that Lyprinol probably does no major harm.