Dataset Information

Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy.

ABSTRACT: We previously reported that a 4- to 6-week low-fat fish oil (LFFO) diet did not affect serum insulin-like growth factor (IGF)-1 levels (primary outcome) but resulted in lower omega-6 to omega-3 fatty acid ratios in prostate tissue and lower prostate cancer proliferation (Ki67) as compared with a Western diet. In this post hoc analysis, the effect of the LFFO intervention on serum pro-inflammatory eicosanoids, leukotriene B4 (LTB4) and 15-S-hydroxyeicosatetraenoic acid [15(S)-HETE], and the cell-cycle progression (CCP) score were investigated. Serum fatty acids and eicosanoids were measured by gas chromatography and ELISA. CCP score was determined by quantitative real-time reverse transcriptase PCR (RT-PCR). Associations between serum eicosanoids, Ki67, and CCP score were evaluated using partial correlation analyses. BLT1 (LTB4 receptor) expression was determined in prostate cancer cell lines and prostatectomy specimens. Serum omega-6 fatty acids and 15(S)-HETE levels were significantly reduced, and serum omega-3 levels were increased in the LFFO group relative to the Western diet group, whereas there was no change in LTB4 levels. The CCP score was significantly lower in the LFFO compared with the Western diet group. The 15(S)-HETE change correlated with tissue Ki67 (R = 0.48; P < 0.01) but not with CCP score. The LTB4 change correlated with the CCP score (r = 0.4; P = 0.02) but not with Ki67. The LTB4 receptor BLT1 was detected in prostate cancer cell lines and human prostate cancer specimens. In conclusion, an LFFO diet resulted in decreased 15(S)-HETE levels and lower CCP score relative to a Western diet. Further studies are warranted to determine whether the LFFO diet antiproliferative effects are mediated through the LTB4/BLT1 and 15(S)-HETE pathways.

SUBMITTER: Galet C

PROVIDER: S-EPMC3947245 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy.

Galet Colette C Gollapudi Kiran K Stepanian Sevan S Byrd Joshua B JB Henning Susanne M SM Grogan Tristan T Elashoff David D Heber David D Said Jonathan J Cohen Pinchas P Aronson William J WJ

Cancer prevention research (Philadelphia, Pa.) 20131029 1

We previously reported that a 4- to 6-week low-fat fish oil (LFFO) diet did not affect serum insulin-like growth factor (IGF)-1 levels (primary outcome) but resulted in lower omega-6 to omega-3 fatty acid ratios in prostate tissue and lower prostate cancer proliferation (Ki67) as compared with a Western diet. In this post hoc analysis, the effect of the LFFO intervention on serum pro-inflammatory eicosanoids, leukotriene B4 (LTB4) and 15-S-hydroxyeicosatetraenoic acid [15(S)-HETE], and the cell- ...[more]

PMID: 24169960

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Project description:An emerging field of research describes the role of preoperative health behaviours, known as prehabilitation. The preoperative period may be a more physically and emotionally salient time to introduce and foster chronic adherence to health behaviours, such as exercise, in patients compared to post-treatment during recovery. Moreover, physical and psychosocial improvements during the preoperative period may translate into an enhanced recovery trajectory with reduced operative complications and postoperative adverse effects. No studies have assessed prehabilitation for men with prostate cancer undergoing radical prostatectomy.This is a multi-centre, pilot randomized control trial conducted at two Canadian urban teaching hospitals. 100 men undergoing radical prostatectomy for prostate cancer with no contraindications to exercise will be recruited and randomized to the prehabiliation program or usual care. Prehabilitation participants will engage in a preoperative, individualized exercise program including pelvic floor muscle strengthening instructions and a healthy lifestyle guide for men with prostate cancer. These participants will be asked to engage in 60 minutes of home-based, unsupervised, moderate-intensity exercise on 3-4 days per week. Usual care participants will receive the same pelvic floor muscle strengthening instructions and healthy lifestyle guide only. We will assess the feasibility of conducting an adequately powered trial of the same design via recruitment rate, programmatic adherence/contamination, attrition, and safety. Estimates of intervention efficacy will be captured through measurements at baseline (4-8 weeks preoperatively), within 1 week prior to surgery, and postoperatively at 4, 12, and 26 weeks. Efficacy outcomes include: fatigue, quality of life, urinary incontinence, physical fitness, body composition, aerobic fitness, pain, and physical activity volume.The primary outcome of this study is to determine the feasibility of conducting a full-scale, randomized controlled trial of prehabilitation versus usual care and to estimate effect sizes that will inform sample size determinations for subsequent trials in this field. To our knowledge, this is the first study to examine a structured presurgical exercise program for men undergoing radical prostatectomy for prostate cancer. This trial will advance our understanding of strategies to efficiently and effectively use the preoperative period to optimize postoperative recovery.Clinicaltrials.gov Identifier: NCT02036684.

Project description:BACKGROUND: The controversies concerning possible overtreatment of prostate cancer, highlighted by debate over PSA screening, have highlighted active surveillance (AS) as an alternative management option for appropriate men. Regional differences in the underlying prevalence of PSA testing may alter the pre-test probability for high-risk disease, which can potentially interfere with the performance of selection criteria for AS. In a multicentre study from three different countries, we examine men who were initially suitable for AS according to the Toronto and Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, that underwent radical prostatectomy (RP) in regards to:1.the proportion of pathological reclassification(Gleason score ≥7, ≥pT3 disease),2.predictors of high-risk disease,3.create a predictive model to assist with selection of men suitable for AS. METHODS: From three centres in the United Kingdom, Canada and Australia, data on men who underwent RP were retrospectively reviewed (n=2329). Multivariable logistic regression was performed to identify predictors of high-risk disease. A nomogram was generated by logistic regression analysis, and performance characterised by receiver operating characteristic curves. RESULTS: For men suitable for AS according to the Toronto (n=800) and PRIAS (410) criteria, the rates for upgrading were 50.6, 42.7%, and upstaging 17.6, 12.4%, respectively. Significant predictors of high-risk disease were:•Toronto criteria: increasing age, cT2 disease, centre of diagnosis and number of positive cores.•PRIAS criteria: increasing PSA and cT2 disease.Cambridge had a high pT3a rate (26 vs 12%). To assist selection of men in the United Kingdom for AS, from the Cambridge data, we generated a nomogram predicting high-risk features in patients who meet the Toronto criteria (AUC of 0.72). CONCLUSION: The proportion of pathological reclassification in our cohort was higher than previously reported. Care must be used when applying the AS criteria generated from one population to another. With more stringent selection criteria, there is less reclassification but also fewer men who may benefit from AS.

Project description:BackgroundSeveral biologic mechanisms, including inflammation and immune changes, have been proposed to explain the role of obesity in prostate cancer (CaP) progression. Compared to men of a healthy weight, overweight and obese men are more likely to have CaP recurrence post-prostatectomy. Obesity is related to inflammation and immune dysregulation; thus, weight loss may be an avenue to reduce inflammation and reverse these immune processes.ObjectivesThis study explores the reversibility of the biological mechanisms through intentional weight loss using a comprehensive weight management program in men undergoing prostatectomy. Outcomes include blood and tissue biomarkers, microtumor environment gene expression, inflammation markers and Dietary Inflammatory Index (DII) scores.MethodsTwenty overweight men undergoing prostatectomy participated in this study. Fifteen men chose the intervention and 5 men chose the nonintervention group. The intervention consisted of a comprehensive weight loss program prior to prostatectomy and a weight maintenance program following surgery. Prostate tissue samples were obtained from diagnostic biopsies before the intervention and prostatectomy samples after weight loss. Blood samples and diet records were collected at baseline, pre-surgery after weight loss and at study end after weight maintenance. Immunohistochemistry and NanoString analysis were used to analyze the tissue samples. Flow cytometry was used to assess circulating immune markers. Inflammation markers were measured using Luminex panels.ResultsThe intervention group lost >5% body weight prior to surgery. DII scores improved during the weight loss intervention from baseline to pre-surgery (P = 0.002); and between group differences were significant (P = 0.02). DII scores were not associated with IL-6 nor hsCRP. In the intervention, CXCL12, CXCR7, and CXCR4 (C-X-C motif chemokine ligand/receptor) and Ki67 expression decreased in the prostate tissue from biopsy to surgery (P = 0.06), yet plasma CXCL12 increased during the same timeframe (P = 0.009). The downregulation of several genes (FDR<0.001) was observed in the intervention compared to the non-intervention. Changes in immune cells were not significant in either group.ConclusionThis feasibility study demonstrates that in overweight men with localized CaP, weight loss alters blood, and tissue biomarkers, as well as tumor gene expression. More research is needed to determine the biological and clinical significance of these findings.

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Project description:BackgroundSeveral studies have investigated the relationship between experience measured by caseload and oncological outcomes, economics, and access to care for prostate cancer care. Oncological outcomes have been limited to biochemical failure after radical prostatectomy. Questions remain regarding the more definitive measures of outcomes and their relationship with caseload.MethodsThe National Cancer Database was used to investigate the outcomes of radical prostatectomy in the United States. With overall survival (OS) as the primary outcome, the relationship between the facility annual caseload (FAC) for all prostate cancer encounters and the facility annual surgical caseload (FASC) for those requiring radical prostatectomy was examined with a Cox proportional hazards model. Four volume groups were defined by caseload: <50th percentile (volume group 1 [VG1]), 50th to 74th percentiles (volume group 2 [VG2]), 75th to 89th percentiles (volume group 3 [VG3]), and ≥90th percentile (volume group 4 [VG4]). By FAC/FASC, 11%/8%, 17%/18%, 25%/26%, and 47%/49% of patients were treated in VG1 through VG4, respectively.ResultsBetween 2004 and 2014, 488,389 patients underwent radical prostatectomy. At a median follow-up of 60.75 months, the median OS was not reached. There was a significant OS benefit as the caseload increased. For FAC, the adjusted OS difference between VG1 and VG4 at 90th percentile survivorship reached 13.2 months (hazard ratio [HR], 1.30; 95% CI, 1.23-1.36; P < .0001). For FASC, this was 11.3 months (HR, 1.25; 95% CI, 1.192-1.321; P < .0001).ConclusionsThere is a statistically significant OS advantage from performing radical prostatectomy at a facility with a high annual caseload. Caseload measured by all prostate cancer encounters is a better predictor of favorable outcomes than the number of surgeries performed at a facility.Lay summaryAn in-depth analysis of 488,389 cases of radical prostatectomy performed in more than 1000 facilities over a 10-year period showed better survival when surgery was performed in facilities with more experience and greater caseload. A survival difference of up to 13 months was observed when comparing patients treated at less experienced versus more experienced centers. Experience across all stages of prostate cancer was a stronger predictor of survival outcome than just the number of surgeries performed.

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Dataset Information

Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy.

Publications

Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy.

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