What Can Surrogate Tissues Tell Us about the Oxidative Stress Status of the Prostate? A Hypothesis-Generating In-Vivo Study

BACKGROUND: Prostatic oxidative stress (OS) is androgen-regulated and a key event in the development of prostate cancer (PC). Thus, reducing prostatic OS is an attractive target for PC prevention strategies. We sought to determine if the individual's prostatic OS status can be determined by examining the OS in surrogate androgen regulated tissues from the same host. METHODOLOGY/PRINCIPAL FINDINGS: Adult male rats were divided equally into three groups: (A-) underwent bilateral orchiectomy, (A+) received continuous testosterone supplementation or (C) were eugonadal. Serum testosterone, 8-hydroxy-2-deoxyguanosine (8-OHdG) and anti-oxidative capacity (AOC) were determined after 72 hrs and the prostate, salivary glands and the hair follicles' Dermal Papillary Cells (DPC) from each animal were harvested, embedded into tissue microarray and examined for the expression of 8-OHdG by immuno-staining. Multi-variate regression was used to analyze inter-individual differences in OS staining within each androgen group and if there was a correlation between serum testosterone, 8-OHdG or AOC and Prostatic OS in tissues of same host. At the group level, 8-OHdG staining intensity directly correlated with serum testosterone levels in all three target tissues (p>0.01, Mann-Whitney Test). Although different levels of prostatic OS were noted between rats with similar serum testosterone levels and similar systemic OS measurements (p<0.01), there were no intra-individual differences between the OS status of the prostate and DPC (p<0.05). CONCLUSIONS/SIGNIFICANCE: The level of prostatic OS is correlated with the OS of hair follicles and salivary glands, but not systemic OS. Moreover, systemic AOC negatively correlates with both prostatic and hair follicle OS. This suggests that hair follicle and salivary gland OS can serve as surrogate markers for the efficiency of OS reduction. This has tremendous potential for the rational evaluation of patient response to prevention strategies

Metabolic features of clear-cell renal cell carcinoma: mechanisms and clinical implications

Central to the malignant behaviour that endows cancer cells with growth advantage is their unique metabolism. Cancer cells can process nutrient molecules differently from normal cells and use it to overcome stress imposed on them by various therapies. This metabolic conversion is controlled by specific genetic mutations that are associated with activation of oncogenes and loss of tumour suppressor proteins. Understanding these processes is important as it can lead to the discovery of biomarkers that can predict the aggressiveness of the disease and its response to therapy, and even more importantly, to the development of novel therapeutics. A classic tumour in this respect is clear-cell renal cell carcinoma (RCC). In this review, we will begin with a brief summary of normal cellular bioenergetic pathways, which will be followed by a description of the characteristic metabolism of glucose and lipids in clear-cell RCC cells and its clinical implications. Data relating to the potential effect of dietary nutrients on RCC will also be reviewed along with potential therapies targeted at interrupting specific metabolic pathways in clear-cell RCC

Experimental data per individual rat.

<p>Please note the lack of correlation between serum testosterone level and serum 8-OHdG levels and tissue expression of OS.</p

Inter-individual differences and intra-individual similarities in the castrated rats.

<p>Inter-individual variability in serum OS and target tissue 8-OHdG staining in rats with similar (castrated) levels of testosterone.</p

Serum testosterone (A), anti-oxidative capacity (B), and 8-OHdG levels (c) per treatment group.

<p>Results are shown as mean +/− S.D. P values were calculated using a two-tailed t-test.</p

Mean, median and range of several factors measured.

<p>Serum testosterone, 8-OHdG and global anti-oxidative capacity (gAOC) per experimental group. Values were rounded to the nearest tenth for all measurements and only the ranges are shown with 2 decimal places to show the variation in values.</p