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dc.contributor.advisor Pizzo, Salvatore V en_US
dc.contributor.author Mavropoulos, John Christakis en_US
dc.date.accessioned 2010-05-10T19:53:53Z
dc.date.available 2010-05-10T19:53:53Z
dc.date.issued 2008 en_US
dc.identifier.uri http://hdl.handle.net/10161/2263
dc.description Dissertation en_US
dc.description.abstract <p>Glucose metabolism remains an intensely explored topic of cancer biology since the initial discoveries of Otto Warburg nearly 80 years ago. Many solid tumors metabolize glucose primarily to lactate despite the availability of oxygen, revealing a dependence on glycolysis that may serve as a basis for targeted therapy. In particular, a diet devoid of carbohydrate may minimize the growth capabilities of glucose-dependent cancers. As our interests lie in prostate cancer, we examined whether a ketogenic diet devoid of carbohydrate (NCKD) would reduce the growth rate of tumors derived from human prostate cancer cell lines in a murine xenograft model.</p> <p>Our initial experiments utilized the LAPC-4 cell line, a human androgen-sensitive prostate cancer cell line, in a SCID-mouse xenograft model to determine the effects of an NCKD on tumor growth and animal survival relative to two other diets: (1.) a Western-type diet (WD) reflecting consumptions patterns of men diagnosed with prostate-cancer in the Western world and (2.) a low-fat diet (LFD) representing the present standard of care. Following this study, we conducted a second study utilizing a different human prostate cancer cell line (LNCaP) in order to assess whether our initial observations were robust across multiple prostate cancer tumor models and to also further explore the molecular underpinnings of our observations. Both studies revealed the NCKD leads to a reduction in tumor growth rate and greater overall mouse survival relative to the WD. In addition, the NCKD was equivalent in these parameters to the LFD. We also observed key associations between survival and extent of urinary ketosis as well as favorable changes in insulin and insulin-like growth factor-1 (IGF-1) and gene expression that would be predictive of prolonged survival in mice consuming the NCKD.</p> <p>We believe these data provide compelling evidence to consider a potential therapeutic role for dietary carbohydrate restriction in prostate cancer. We hope these results ultimately serve as a basis to conduct future clinical trials assessing whether dietary carbohydrate restriction, either alone or in combination with more conventional therapies, provides clinicians with an additional weapon against prostate cancer.</p> en_US
dc.format.extent 540322 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Health Sciences, Pathology en_US
dc.subject Carbohydrate en_US
dc.subject Prostate cancer
dc.subject IGF axis
dc.subject Ketogenic diet
dc.title Dietary Carbohydrate Restriction Slows Prostate Tumor Growth en_US
dc.type Dissertation en_US
dc.department Pathology en_US
duke.embargo.months 24 en_US
dc.date.accessible 2010-05-18T05:00:32Z

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