Publications [#178155] of Gayathri R Devi

Papers Published

1. JC Mavropoulos, WC Buschemeyer 3rd, AK Tewari, D Rokhfeld, M Pollak, Y Zhao, PG Febbo, P Cohen, D Hwang, G Devi, W Demark-Wahnefried, EC Westman, BL Peterson, SV Pizzo, SJ Freedland, The effects of varying dietary carbohydrate and fat content on survival in a murine LNCaP prostate cancer xenograft model., Cancer prevention research (Philadelphia, Pa.), vol. 2 no. 6 (June, 2009), pp. 557-65, ISSN 1940-6215 [doi]
   (last updated on 2013/05/16)

   Abstract:
   OBJECTIVE: Numerous dietary factors elevate serum levels of insulin and insulin-like growth factor I (IGF-I), both potent prostate cancer mitogens. We tested whether varying dietary carbohydrate and fat, without energy restriction relative to comparison diets, would slow tumor growth and reduce serum insulin, IGF-I, and other molecular mediators of prostate cancer in a xenograft model. METHODS: Individually caged male severe combined immunodeficient mice (n = 130) were randomly assigned to one of three diets (described as percent total calories): very high-fat/no-carbohydrate ketogenic diet (NCKD: 83% fat, 0% carbohydrate, 17% protein), low-fat/high-carbohydrate diet (LFD: 12% fat, 71% carbohydrate, 17% protein), or high-fat/moderate-carbohydrate diet (MCD: 40% fat, 43% carbohydrate, 17% protein). Mice were fed to maintain similar average body weights among groups. Following a preliminary feeding period, mice were injected with 1 x 10(6) LNCaP cells (day 0) and sacrificed when tumors were >or=1,000 mm(3). RESULTS: Two days before tumor injection, median NCKD body weight was 2.4 g (10%) and 2.1 g (8%) greater than the LFD and MCD groups, respectively (P < 0.0001). Diet was significantly associated with overall survival (log-rank P = 0.004). Relative to MCD, survival was significantly prolonged for the LFD (hazard ratio, 0.49; 95% confidence interval, 0.29-0.79; P = 0.004) and NCKD groups (hazard ratio, 0.59; 95% confidence interval, 0.37-0.93; P = 0.02). Median serum insulin, IGF-I, IGF-I/IGF binding protein-1 ratio, and IGF-I/IGF binding protein-3 ratio were significantly reduced in NCKD relative to MCD mice. Phospho-AKT/total AKT ratio and pathways associated with antiapoptosis, inflammation, insulin resistance, and obesity were also significantly reduced in NCKD relative to MCD tumors. CONCLUSIONS: These results support further preclinical exploration of carbohydrate restriction in prostate cancer and possibly warrant pilot or feasibility testing in humans.

   Keywords:
   Adenocarcinoma • Animals • Apoptosis • Blood Glucose • Cell Line, Tumor • Diet, Carbohydrate-Restricted* • Dietary Carbohydrates • Dietary Fats • Disease Progression • Fatty Liver • Gene Expression Regulation, Neoplastic • Humans • Insulin • Insulin Resistance • Insulin-Like Growth Factor Binding Protein 1 • Insulin-Like Growth Factor Binding Protein 3 • Insulin-Like Growth Factor I • Ketogenic Diet • Ketones • Male • Mice • Mice, SCID • Prostatic Neoplasms • Proto-Oncogene Proteins c-akt • Random Allocation • Xenograft Model Antitumor Assays • administration & dosage • analysis • blood • diet therapy* • drug effects • etiology • genetics • pathology • therapeutic use* • toxicity* • transplantation • urine