| Autor: |
Khachigian LM, Cai H, Moloney FJ, Parish CR, Chong BH, Stocker R, Barnetson RS, Halliday GM |
| Jazyk: |
angličtina |
| Zdroj: |
Oncotarget [Oncotarget] 2012 Jun; Vol. 3 (6), pp. 594-5. |
| DOI: |
10.18632/oncotarget.549 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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