Abstract:Background: Adipocytokines may mediate the association between adiposity and lethal prostate cancer outcomes.
Methods: In the Physicians’ Health Study, we prospectively examined the association of prediagnostic plasma concentrations of adiponectin and leptin with risk of developing incident prostate cancer (654 cases diagnosed 1982–2000 and 644 age-matched controls) and, among cases, risk of dying from prostate cancer by 2007.
Results: Adiponectin concentrations were not associate… Show more
“…10,11,14 Maximizing adiponectin signaling appears logical as a translational possibility in PC. Unfortunately, treatment with adiponectin per se is impractical, as it has a short half-life, is present at high circulating levels, and largescale production of the native forms of full-length adiponectin with all post-translational modifications is a difficult task.…”
Section: Discussionmentioning
confidence: 99%
“…8,9 Several case-control studies have documented that lower levels of adiponectin are associated with increased incidence and aggressiveness of PC. [10][11][12][13][14] However, the mechanisms responsible for the tumorsuppressive effects of adiponectin are not clear.…”
BACKGROUND: Emerging data suggest that obesity increases the risk of aggressive prostate cancer (PC), but the mechanisms underlying this relationship remain to be fully elucidated. Oxidative stress (OS) is a key process in the development and progression of PC. Adiponectin, an adipocyte-specific hormone, circulates at relatively high levels in healthy humans, but at reduced levels in obese subjects. Moreover, case-control studies also document lower levels of serum adiponectin in PC patients compared with healthy individuals.
METHODS:Human 22Rv1 and DU-145 PC cell lines were examined for the generation of OS and detoxification of reactive oxygen species after treatment with adiponectin. Normality was confirmed using the Shapiro-Wilk test and results were analyzed using a one-way analysis of variance.
RESULTS:We demonstrate that adiponectin increased cellular anti-oxidative defense mechanisms and inhibited OS in a significant and dose-dependent manner. We show that adiponectin treatment decreased the generation of superoxide anion in both cell lines, whereas the transcript levels of NADPH oxidase (NOX)2 and NOX4 increased. We also found indications of an overall anti-oxidative effect, as the total anti-oxidative potential, catalase activity and protein levels, and manganese superoxide dismutase protein levels increased significantly (Po0.05) in both cell lines after treatment with adiponectin.CONCLUSION: Lower levels of adiponectin in obese individuals may result in higher levels of prostatic OS, which may explain the clinical association between obesity, hypoadiponectinemia and PC.
“…10,11,14 Maximizing adiponectin signaling appears logical as a translational possibility in PC. Unfortunately, treatment with adiponectin per se is impractical, as it has a short half-life, is present at high circulating levels, and largescale production of the native forms of full-length adiponectin with all post-translational modifications is a difficult task.…”
Section: Discussionmentioning
confidence: 99%
“…8,9 Several case-control studies have documented that lower levels of adiponectin are associated with increased incidence and aggressiveness of PC. [10][11][12][13][14] However, the mechanisms responsible for the tumorsuppressive effects of adiponectin are not clear.…”
BACKGROUND: Emerging data suggest that obesity increases the risk of aggressive prostate cancer (PC), but the mechanisms underlying this relationship remain to be fully elucidated. Oxidative stress (OS) is a key process in the development and progression of PC. Adiponectin, an adipocyte-specific hormone, circulates at relatively high levels in healthy humans, but at reduced levels in obese subjects. Moreover, case-control studies also document lower levels of serum adiponectin in PC patients compared with healthy individuals.
METHODS:Human 22Rv1 and DU-145 PC cell lines were examined for the generation of OS and detoxification of reactive oxygen species after treatment with adiponectin. Normality was confirmed using the Shapiro-Wilk test and results were analyzed using a one-way analysis of variance.
RESULTS:We demonstrate that adiponectin increased cellular anti-oxidative defense mechanisms and inhibited OS in a significant and dose-dependent manner. We show that adiponectin treatment decreased the generation of superoxide anion in both cell lines, whereas the transcript levels of NADPH oxidase (NOX)2 and NOX4 increased. We also found indications of an overall anti-oxidative effect, as the total anti-oxidative potential, catalase activity and protein levels, and manganese superoxide dismutase protein levels increased significantly (Po0.05) in both cell lines after treatment with adiponectin.CONCLUSION: Lower levels of adiponectin in obese individuals may result in higher levels of prostatic OS, which may explain the clinical association between obesity, hypoadiponectinemia and PC.
“…Physical activity also increases adiponectin levels, which has anti-inflammatory and mitogenic actions, 36 and men with the highest compared with lowest quintile of adiponectin concentration had a 61% lower risk of PCa mortality (HR, 0.39; 95% CI, 0.17 to 0.85; P trend Ͻ .02). 37 Physical activity also affects the innate immune system. 38 Exercise in patients with breast cancer was associated with improved natural killer cell cytolytic activity, 39 monocyte function, 40 and proportion of circulating granulocytes.…”
A B S T R A C T PurposeTo determine whether higher physical activity after prostate cancer (PCa) diagnosis decreases risk of overall and PCa-specific death.
Patients and MethodsWe evaluated physical activity in relation to overall and PCa mortality among 2,705 men in the Health Professionals Follow-Up Study diagnosed with nonmetastatic PCa observed from 1990 to 2008. Proportional hazards models were used to evaluate physical activity and time to overall and PCa-specific death.
ResultsAmong men who lived at least 4 years after their postdiagnosis physical activity assessment, we documented 548 deaths, 20% of which were a result of PCa. In multivariable analysis, men who were physically active had lower risk of all-cause mortality (P trend Ͻ .001) and PCa mortality (P trend ϭ .04). Both nonvigorous activity and vigorous activity were associated with significantly lower overall mortality. Those who walked Ն 90 minutes per week at a normal to very brisk pace had a 46% lower risk of all-cause mortality (hazard ratio [HR] 0.54; 95% CI, 0.41 to 0.71) compared with shorter durations at an easy walking pace. Men with Ն 3 hours per week of vigorous activity had a 49% lower risk of all-cause mortality (HR, 0.51; 95% CI, 0.36 to 0.72). For PCa-specific mortality, brisk walking at longer durations was suggestively inverse but not statistically significant. Men with Ն 3 hours per week of vigorous activity had a 61% lower risk of PCa death (HR, 0.39, 95% CI, 0.18 to 0.84; P ϭ .03) compared with men with less than 1 hour per week of vigorous activity. Men exercising vigorously before and after diagnosis had the lowest risk.
ConclusionIn men with PCa, physical activity was associated with lower overall mortality and PCa mortality. A modest amount of vigorous activity such as biking, tennis, jogging, or swimming for Ն 3 hours a week may substantially improve PCa-specific survival.
J Clin
“…Adiponectin (2) and insulin (3) are hormones whose circulating levels are influenced by obesity and may play a role in carcinogenesis. The association of adiponectin with prostate cancer was investigated by two prospective studies (4,5), which yielded conflicting results. Whereas Li and colleagues (4) reported a significant inverse association of adiponectin with both high grade and lethal prostate cancer, Touvier and colleagues (5) found no significant association with prostate cancer overall.…”
Background: Obesity is associated with a higher risk of aggressive prostate cancer and alters circulating levels of insulin and adiponectin, two hormones that influence biologic processes implicated in carcinogenesis. Results of some studies showed associations of circulating levels of adiponectin, insulin, and c-peptide (a marker of insulin secretion) with aggressive prostate cancer, but the size of these studies was limited.Methods: A nested case-control study of 272 aggressive prostate cancer cases [Gleason score !7 (4þ3) or T3-T4] and 272 age-and race-matched controls from the Cancer Prevention Study II Nutrition Cohort was conducted to determine the associations of prediagnostic plasma levels of c-peptide and adiponectin with risk of aggressive prostate cancer.Results: Neither circulating adiponectin nor c-peptide was associated with risk of aggressive prostate cancer. In analyses of the highest-risk aggressive prostate cancer (Gleason score !8 or T3-T4), the highest quartile of c-peptide, compared with the lowest, was associated with an OR of 1.41 [95% confidence interval (CI), 0.72-2.78].Conclusions: Our findings provide no support for the hypothesis that adiponectin is associated with risk of aggressive prostate cancer but a possible association of high levels of c-peptide with particularly high-risk prostate cancer cannot be ruled out.Impact: These results indicate that changes in circulating levels of adiponectin and c-peptide do not play an important role in risk of aggressive prostate cancer. Cancer Epidemiol Biomarkers Prev; 23(5); 890-2. Ó2014 AACR.
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