Clinical significance of the leptin and leptin receptor expressions in prostate tissues

Aim： To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia （BPH） and prostate cancer （PCa）, and to investigate whether they are associated with the development and progression of PCa. Methods： hnmunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups： localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index （BMI） and PCa. Results： The percentage of the leptin expression in PCa was significantly higher than that in BPH （P 〈 0.01）. For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa （P 〈 0.05）. Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa （Gleason score ≤6） and poorly differentiated PCa （Gleason score 8-10） （P 〈 0.05）. The relation between the leptin expression level in PCa and the BMI was not remarkable （P = 0.447）. Conclusion： Our results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa.

Relationship between insulin resistance, obesity and serum prostate-specific antigen levels in healthy men

The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen （PSA） levels in healthy men with serum PSA level below 4 ng mL-1. The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment （HOMA [fasting glucose × fasting insulin]/22.5） and quantitative insulin sensitivity check index （QUICK/; 1/[log （fasting insulin） ＋ log （fasting glucose）]）. Age-adjusted body mass index （BMI） was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance （ANOVA） test and Duncan＇s multiple comparison test （P 〈 0.001）, but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICK/（P 〈 0.001）. Age, BMI, insulin resistance by HOMA or QUICK/were significantly independent variables to serum PSA level in a multivariate linear regression analysis （P 〈 0.001）. Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.

Krill oil ameliorates benign prostatic hyperplasia by regulating G1-phase cell cycle arrest and altering signaling pathways and benign prostatic hyperplasia-associated markers

Krill oil(KO)exhibits various biological activities,such as anti-inflammatory and antitumor effects.However,the inhibitory effects of benign prostatic hyperplasia(BPH)in vitro and in vivo have not yet been studied.This study investigated the anti-BPH effects of KO extracted by an enzymatic hydrolysis method.KO treatment inhibited the proliferation of WMPY-1 and BPH-1 cells by induction of G0/G1 phase arrest through the modulation of positive and negative regulators in both prostate cell types.KO treatment stimulated phosphorylation of c-Jun N-terminal kinase(JNK)and p38 signaling.In addition,KO changed the expression of BPH-related markers(5α-reductase,androgen receptor,FGF,Bcl-2,and Bax)and the activity of the proliferation-mediated NF-κB binding motif.KO-induced levels of proliferation-mediated molecules of prostate cells were attenuated in the presence of siRNA-specific p-38(si-p38)and JNK(si-JNK).Furthermore,the administration of KO alleviated prostate size and weight and the cell layer thickness of prostate glands in a testosterone enanthate-induced BPH rat model.KO treatment altered the level of dihydrotestosterone in serum and the expression levels of BPH-related markers in prostate tissues.Finally,KO-mediated inhibition of prostatic growth was validated by histological analysis.These results suggest that KO has an inhibitory effect on BPH in prostate cells in vitro and in vivo.Thus,KO might be a potential prophylactic or therapeutic agent for patients with BPH.

Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population

In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer （PCa） in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 singie-nucleotide polymorphism （SNP） database variants detected, 129 were reported in two Asian groups （Han Chinese and Japanese） in the HapMap database. Only 21 polymorphisms of CYP17A1, CYP3A4, and CYP3A43 were selected based on linkage disequilibrium in Asians （d = 1）, locations （SNPs in exons were preferred）, and amino acid changes and were assessed. In addition, we performed haplotype analysis for the 21 SNPs in CYP17A1, CYP3A4, and CYP3A43 genes. To determine the association between genotype and haplotype distributions of patients and controls, logistic analyses were carried out, controlling for age. Twelve sequence variants and five major haplotypes were identified in CYP17A1. Five sequence variants and two major haplotypes were identified in CYP3A4. Four sequence variants and four major haplotypes were observed in CYP3A43. CYP17A1 haplotype-2 （Ht-2） （odds ratio [OR], 1.51; 95% confidence interval [Cl], 1.04-2,18） was associated with PCa susceptibility. CYP3A4 Ht-2 （OR. 1.87; 95% CI. 1.02-3.43） was associated with PCa metastatic potential according to tumor stage, rs17115149 （OR： 1.96; 95% Ch 1.04-3.68） and CYP17A1 Ht-4 （OR： 2.01; 95% Ch 1.07-4.11） showed a significant association with histologic aggressiveness according to Gleason score. Genetic variants of CYP17A1 and CYP3A4 may play a role in the development of PCa in Korean men.