Epidemiologic studies have demonstrated an inverse association between flavonoid intake and prostate cancer (PCa) risk. The East Asian diet is very high in flavonoids and, correspondingly, men in China and Japan have the lowest incidence of PCa worldwide. There are thousands of different naturally occurring and synthetic flavonoids. However, only a few have been studied in PCa. Our aim was to identify novel flavonoids with antiproliferative effect in PCa cell lines, as well as determine their effects on cell cycle. We have screened a representative subgroup of 26 flavonoids for antiproliferative effect on the human PCa (LNCaP and PC3), breast cancer (MCF-7), and normal prostate stromal cell lines (PrSC). Using a fluorescence-based cell proliferation assay (Cyquant), we have identified five flavonoids, including the novel compounds 2,2 0 -dihydroxychalcone and fisetin, with antiproliferative and cell cycle arresting properties in human PCa in vitro. Most of the flavonoids tested exerted antiproliferative effect at lower doses in the PCa cell lines compared to the non-PCa cells. Flow cytometry was used as a means to determine the effects on cell cycle. PC3 cells were arrested in G2/M phase by flavonoids. LNCaP cells demonstrated different cell cycle profiles. Further studies are warranted to determine the molecular mechanism of action of 2,2 0 -DHC and fisetin in PCa, and to establish their effectiveness in vivo.

This analysis of cryptorchid testes in postpubertal male subjects confirms that the majority cannot contribute to fertility, have significant malignant potential and may undergo torsion. Therefore, orchiectomy remains the treatment of choice for the majority of postpubertal male subjects presenting with unilateral cryptorchidism.

Purpose: Increased levels of serum human kallikrein-2 (hK2) and an hK2 gene (KLK2) variant are positively associated for prostate cancer, but the relationships between them remain unclear. We examined five variants of the KLK2 gene to further define its relevance to prostate cancer susceptibility and hK2 levels. Experimental Design: We genotyped 645 men with biopsy-proven prostate cancer (cases) and 606 males with biopsies negative for prostate cancer (controls) for five additional single nucleotide polymorphisms (SNP) across the KLK2 gene and also tested for serum hK2 levels. These SNPs were identified from sequencing the KLK2 gene among 20 patients with aggressive prostate cancer. Odds ratios (OR) for prostate cancer detection and haplotype analysis were done.Results: Among the SNPs studied, the A allele of the KLK2-SNP1 (G > A, rs2664155) and the Tallele of the KLK2-SNP5 (C > T, rs198977) polymorphisms showed positive associations with prostate cancer, adjusted ORs for KLK2-SNP1AG and AA genotypes being 1.4 [95% confidence interval (95% CI), 1.2-1.8; P = 0.002] and for KLK2-SNP5 TTor CTgenotypes being 1.3 (95% CI, 1.1-1.6; P = 0.05). Haplotype analyses also revealed a significant association between prostate cancer and the haplotype containing both risk alleles (ACCTT), OR being 5.1 (95% CI, 1.6-6.5; P = 0.005). Analysis of serum hK2 revealed hK2 levels to be significantly increased in association with KLK2-SNP1 AA and AG risk genotypes compared with the GG genotype (P = 0.001) and also in association with the ACCTT risk haplotype compared with the most common non-risk haplotype (P = 0.05). Conclusions: These findings suggest a role for the KLK2 gene in prostate cancer susceptibility and imply that this role may be realized at least in part by the induction of increases in hK2 production.Several single nucleotide polymorphisms (SNP) have been evaluated with regard to the risk of prostate cancer. However, to date, no genetic test is used in clinical practice to evaluate prostate cancer risk. Associations are often not reproducible, and the lack of correlation between SNPs and the protein expression or activity is of concern.Our approach is to evaluate the use of candidate SNPs in predicting the presence of prostate cancer at the time of prostate biopsy (1 -3). We recently reported a positive association between a C for T substitution (rs198977) within the human kallikrein type-2 (hK2) gene (KLK2) and prostate cancer risk (3). The KLK2 gene is part of the kallikrein gene family, which also includes prostate-specific antigen (PSA; KLK3 gene; ref. 4). The KLK2 gene is located on chromosome 19q13.41. It consists of five exons and is 5,217 bp in length (226 amino acids; ref. 4). This association [odds ratio (OR), 2.1; 95% confidence interval (95% CI), 1.3-3.5; P = 0.004] was detected using a casecontrol study design on subjects who underwent a prostate biopsy and were found on biopsy to be either positive (cases) or negative (controls) for adenocarcinoma of the prostate.Previously, we and others independe...

This analysis of cryptorchid testes in postpubertal male subjects confirms that the majority cannot contribute to fertility, have significant malignant potential and may undergo torsion. Therefore, orchiectomy remains the treatment of choice for the majority of postpubertal male subjects presenting with unilateral cryptorchidism.