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dc.contributor.authorRobinson, Bracha
dc.descriptionThe file is restricted for YU community access only.en_US
dc.description.abstractPoorly differentiated thyroid carcinomas are aggressive tumors that are often untreatable and fatal. Obatoclax, an anti-cancer drug, suppresses these tumors, but its mechanism of action remains unclear. Since Obatoclax was designed as an inhibitor of antiapoptotic Bcl2 family members, apoptosis is one possible route to cell death. This may be determined through Mcl-1 and Bcl2a1 inhibition, since Mcl-1 and Bcl2a1 are anti-apoptotic proteins consistently overexpressed in thyroid carcinomas. Additionally, Obatoclax may cause cell death through modulation of autophagy. ATG5 is a protein that is necessary for autophagy to occur, and suppression of ATG5 may prevent Obatoclax from effecting tumor suppression. Alternatively, Obatoclax may cause cell death by inducing lysosome degradation. By altering lysosomal acidity with bafilomycin, it can be determined whether Obatoclax acts through degradation of the lysosomes. In this study, Mcl-1 and ATG5 were knocked down, and the data show that these modified cells do not respond differently to Obatoclax than the parent cells, meaning that Obatoclax is able to cause cell death even without Mcl-1 and ATG5. Therefore, Mcl-1 and autophagy are not integral to Obatoclax’s pathway. However, the data indicate that cells treated with bafilomycin show a partial rescue from Obatoclax induced cell death, which indicates that lysosomal de-acidification hampers Obatoclax from killing the cancer cells. This suggests that the lysosomes are involved in Obatoclax’s pathway, and drugs that target the lysosomes may be a novel therapeutic avenue for treating aggressive thyroid tumors.en_US
dc.description.sponsorshipS. Daniel Abraham Honors Programen_US
dc.publisherStern College for Womenen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.subjectThyroid gland -- Cancer -- Treatmenten_US
dc.subjectDissertations, Academicen_US
dc.subjectElectronic booksen_US
dc.titleThe Mechanism Through Which Obatoclax Kills Thyroid Cancer Cellsen_US

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  • Honors Student Theses [208]
    Senior honors theses sponsored by the S. Daniel Abraham Honors Program of Stern College for Women

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Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States