A Nanoparticle Mediated Gene Silencing Approach for the Treatment of Metastatic Ovarian Cancer Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/sn00b379m

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  • Ovarian cancer, “the silent killer,” is one of the deadliest gynecological diseases due to delayed diagnosis, leading to a heavily disseminated and aggressive metastatic cancer. Therapeutic options are limited at stages III-IV of ovarian cancer, in which debulking surgery and cytotoxic chemotherapy remain the mainstays of intervention. However, these therapeutic modalities are not adequate: the 5-year mortality rates for stages III-IV ovarian cancer are extremely abysmal, providing only 17% survival rates for patients after treatment. Therefore, there is a dire need for new therapeutic modalities to treat this disease and improve quality of life of patients as they undergo chemotherapy. PARK7/DJ-1 is an oncogenic driver protein in numerous cancers. DJ-1 plays a fundamental role in the growth, survival, and proliferation in cancer. However, targeting of DJ-1 for therapeutic gain in ovarian cancer has not been previously reported. I have designed a nanoparticle-based platform that delivers DJ-1 siRNA to ovarian cancer cells. This system effectively silences DJ-1 expression and suppresses ovarian cancer growth in vitro and in vivo. Further, I have shown that a knockdown of DJ-1 causes an increase in intracellular reactive oxygen species (ROS), and this renders the cancer cells more vulnerable to agents inducing oxidative stress through multiple signaling pathways.
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Last modified: 04/11/2018

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