Khachigian, Levon M and Cai, Hong and Moloney, Fergal J and Parish, Christopher R and Chong, Beng H and Stocker, Roland and Barnetson, Ross St C and Halliday, Gary M (2012) Destroying c-jun Messenger: new insights into biological mechanisms of DNAzyme function. Oncotarget, 3 (6). pp. 594-5. ISSN 1949-2553 (PMC OA)
Khachigian, Levon M and Cai, Hong and Moloney, Fergal J and Parish, Christopher R and Chong, Beng H and Stocker, Roland and Barnetson, Ross St C and Halliday, Gary M (2012) Destroying c-jun Messenger: new insights into biological mechanisms of DNAzyme function. Oncotarget, 3 (6). pp. 594-5. ISSN 1949-2553 (PMC OA)
Khachigian, Levon M and Cai, Hong and Moloney, Fergal J and Parish, Christopher R and Chong, Beng H and Stocker, Roland and Barnetson, Ross St C and Halliday, Gary M (2012) Destroying c-jun Messenger: new insights into biological mechanisms of DNAzyme function. Oncotarget, 3 (6). pp. 594-5. ISSN 1949-2553 (PMC OA)
Abstract
The study by Cai and co-workers provided novel insights into the mechanism of action of DNAzymes. Dz13 rendered c-jun mRNA unstable, reduced growth factor expression and increased apoptosis in the tumors without apparent induction of oxidative stress. Interestingly, Dz13-mediated tumor decay was more profound in immunocompetent mice syngeneic to the tumor compared with immunocompromised animals. Immunohistological inspection revealed increased immune and inflammatory cells in Dz13-treated tumors in the immunocompetent mice. In addition, Dz13 mediated tumor regression was prevented by the administration of CD4 or CD8 antibodies, which depleted the mice of the respective T cell subsets. Thus, inhibition of tumor growth by a DNAzyme involves the induction of tumor immunity. These findings suggest that c-Jun inhibition in tumors stimulates apoptosis and adaptive immune mechanisms that attack the tumor. Underpinned by a favorable preclinical safety profile, DNAzymes could provide a new treatment option combining both direct and indirect mechanisms to prevent the growth and spread of non-melanoma skin cancer. (No funders listed
Metadata
Subjects: | R Medicine > R Medicine (General) |
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Depositing User: | Repository Administrator |
Date Deposited: | 08 Jan 2016 05:29 |
Last Modified: | 29 Feb 2016 04:44 |