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A Differentiation Therapy for the N2a Neuroblastoma through the Cholesterol Synthesis Pathway

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dc.contributor.advisor Stewart, William en_US Hollis, Paul Ross en_US 2014-06-02T18:51:31Z 2014-06-02T18:51:31Z 2013-08-16 en_US
dc.description.abstract Neuroblastomas are the second most common childhood cancer, claiming 15% of all childhood cancer deaths. To discover a differentiation therapy to treat the cancerous neuroblastoma cell, the elevated activity of the cholesterol synthesis pathway has been investigated. Statin drugs are aggressive inhibitors of the rate limiting enzyme, HMG-CoA reductase, of the cholesterol synthesis pathway. Inhibition of this enzyme eliminates the production of downstream intermediates, along with their entire non-sterol and sterol end products. Add-back experiments exposed that mevinolin co-treatment with cholesterol intermediates mevalonate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate, blocked neurite outgrowths and cells appear unable to differentiate, exhibiting the typical morphology of neuroblastoma cells. However, the add-back of cholesterol (dissolved in 95% ethanol) triggered differentiation of the N2a neuroblastoma cell. This study demonstrates that the N2a neuroblastoma cell differentiates after add-back of cholesterol, implying that the agent(s) of differentiation lies above the production of cholesterol. en_US
dc.publisher Middle Tennessee State University en_US
dc.title A Differentiation Therapy for the N2a Neuroblastoma through the Cholesterol Synthesis Pathway en_US
dc.type Thesis en_US
dc.contributor.committeemember Farone, Anthony en_US
dc.contributor.committeemember Elrod-Erickson, Matthew en_US
dc.thesis.degreelevel Masters en_US
dc.thesis.degreegrantor Middle Tennessee State University en_US
dc.subject.umi Molecular biology en_US
dc.subject.umi Neurosciences en_US
dc.subject.umi Biology en_US M.S. en_US
dc.contributor.department Biology en_US

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