A Differentiation Therapy for the N2a Neuroblastoma through the Cholesterol Synthesis Pathway
A Differentiation Therapy for the N2a Neuroblastoma through the Cholesterol Synthesis Pathway
dc.contributor.advisor | Stewart, William | en_US |
dc.contributor.author | Hollis, Paul Ross | en_US |
dc.contributor.committeemember | Farone, Anthony | en_US |
dc.contributor.committeemember | Elrod-Erickson, Matthew | en_US |
dc.contributor.department | Biology | en_US |
dc.date.accessioned | 2014-06-02T18:51:31Z | |
dc.date.available | 2014-06-02T18:51:31Z | |
dc.date.issued | 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.description.degree | M.S. | en_US |
dc.identifier.uri | http://jewlscholar.mtsu.edu/handle/mtsu/3577 | |
dc.publisher | 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 |
dc.thesis.degreegrantor | Middle Tennessee State University | en_US |
dc.thesis.degreelevel | Masters | en_US |
dc.title | A Differentiation Therapy for the N2a Neuroblastoma through the Cholesterol Synthesis Pathway | en_US |
dc.type | Thesis | en_US |
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