A Novel RNA Helicase Inhibitor to Treat Breast Cancer
Annual rept. 1 Aug 2010-31 Jul 2011
JOHNS HOPKINS UNIV BALTIMORE MD
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During the current funding period, we have done extensive work to prepare and characterize PLGA nanoparticles containing the dual-contrast agent, which will be used to detect delivery and release of NZ51 within the tumor environment. The nanoparticles generated will be used in orthotopic models of breast cancer to visualize the release kinetics of NZ51 and the effect on tumor growth with MRI. In addition, we have generated data to indicate that NZ51 when administered i.p can significantly reduce the growth of primary orthotopic mammary tumors in SCID mice. Additionally, we have demonstrated that in the presence of NZ51, DDX3 is functionally inactive in two breast cancer cell lines, MCF-7 and MDA-MB-231 as demonstrated by functional reporter assays, even though NZ51 decreases turnover of DDX3. This could be due to the fact that binding of NZ51 to DDX3 may have structurally altered DDX3, thus abrogating its functional activity. Finally, we have shown that NZ51 is active under both hypoxic and normoxic conditions, an essential criterion for effective chemotherapy.
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