Diet is thought to play a major role in prostate cancer development and progression, yet little is currently known. Preliminary studies from our laboratory have demonstrated that a diet completely devoid of carbohydrates can slow in vivo prostate cancer growth and appears to act via the insulin-like growth factor (IGF) axis. Recent data from others suggests that resveratrol, a natural phytochemical found in red wine, can slow tumor growth via the same mechanism. We hypothesize that the combination of carbohydrate restriction plus resveratrol , both acting via IGF-axis inhibition, can a ct together to delay prostate cancer growth. To test this hypothesis, we will pursue the following course of study: 1) determine the amount of carbohydrate restriction needed to maximally delay prostate cancer growth;2) eucidate the role of resveratrol in delaying prostate cancer growth and determine the dose which maximally delays tumor growth;and 3) explore the combined effects of carbohydrate restriction and resveratrol supplementation relative to treatment with a Western diet. We believe these studies will better elucidate the role of carbohydrate restriction and resveratrol in modulating in vivo prostate cancer growth and will lay the solid foundation for future preclinical studies for men with prostate cancer. PUBLIC HEALTH STATEMENT Prostate cancer is a major cause of morbidity and mortality among men in the United States. In this proposal, we aim to develop novel non-toxic complementary treatments aimed at slowing prostate cancer progression: dietary modification and phytopharmaceuticals. If these pre-clinical studies are successful, this will lay a solid foundation for future clinical studies among men with prostate cancer, which eventually stand the possibility of radically altering and improving care for men with prostate cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA131235-04
Application #
8115766
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Kim, Young S
Project Start
2008-09-15
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$300,504
Indirect Cost
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Allott, Emma H; Masko, Elizabeth M; Freedland, Alexis R et al. (2018) Serum cholesterol levels and tumor growth in a PTEN-null transgenic mouse model of prostate cancer. Prostate Cancer Prostatic Dis 21:196-203
Allott, E H; Macias, E; Sanders, S et al. (2017) Impact of carbohydrate restriction in the context of obesity on prostate tumor growth in the Hi-Myc transgenic mouse model. Prostate Cancer Prostatic Dis 20:165-171
Alfaqih, Mahmoud A; Nelson, Erik R; Liu, Wen et al. (2017) CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer. Cancer Res 77:1662-1673
Masko, Elizabeth M; Alfaqih, Mahmoud A; Solomon, Keith R et al. (2017) Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model. Prostate 77:446-457
Allott, Emma H; Howard, Lauren E; Song, Hai-Jun et al. (2014) Racial differences in adipose tissue distribution and risk of aggressive prostate cancer among men undergoing radiotherapy. Cancer Epidemiol Biomarkers Prev 23:2404-12
Allott, Emma H; Howard, Lauren E; Cooperberg, Matthew R et al. (2014) Serum lipid profile and risk of prostate cancer recurrence: Results from the SEARCH database. Cancer Epidemiol Biomarkers Prev 23:2349-56
Allott, Emma H; Howard, Lauren E; Cooperberg, Matthew R et al. (2014) Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 114:661-6
Caso, Jorge; Masko, Elizabeth M; Ii, Jean A Thomas et al. (2013) The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model. Prostate 73:449-54
Masko, Elizabeth M; Allott, Emma H; Freedland, Stephen J (2013) The relationship between nutrition and prostate cancer: is more always better? Eur Urol 63:810-20
Osmond, Gregory W; Masko, Elizabeth M; Tyler, Douglas S et al. (2013) In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4'-acetoxy-trans-stilbene in the treatment of human prostate carcinoma and melanoma. J Surg Res 179:e141-8

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