Exercise participation, barriers, and preferences in Korean prostate cancer survivors.

Objective: To identify patterns of physical activity (PA) participation, exercise preference, and barriers of stage 2-3 prostate cancer survivors across cancer trajectories based on selected demographic and medical variables.Design: The current study is a descriptive cross-sectional study which included data from a total of 111 prostate cancer survivors, at Shinchon Severance Hospital, Seoul, Korea. The survey includes PA levels before and after prostate cancer diagnosis, exercise barriers, and preferences.Results: Moderate- to vigorous-intensity PA levels were significantly lower after cancer diagnosis (vigorous PA:41.9 ± 123.1 min/week vs. 4.6 ± 29.8 min/week, p < 0.001; moderate PA: 159.9 ± 240.0 min/week vs. 56.8 ± 129.7 min/week, p < .001) compared to their PA level before cancer diagnosis. Perceived exercise barriers were distinctly different according to participants' age and time since surgery. The two most prevalent exercise barriers among prostate cancer survivors <65 years were lack of time (28.6%) and poor health (26.5%), whereas the exercise barriers for prostate cancer survivors aged ≥65 years were lack of exercise facilities (21.4%) and lack of exercise information (17.9%). Furthermore, within 6 months after surgery, prostate cancer survivors perceived poor health (29.5%) and pain at the surgery site (29.5%) to be the two most prevalent exercise barriers. 6 months after surgery, prostate cancer survivors perceived lack of time (21.3%) and poor health (14.8%) to be the two most prevalent exercise barriers. Walking, pelvic floor and Kegel exercises were three most preferred exercises among prostate cancer survivors in our study, which uniquely differ according to time since surgery.Conclusion: This study showed significant reduction in PA levels among prostate cancer survivors and their perceived exercise barriers were distinct according to their age and time since surgery. Therefore, PA and exercise recommendation should be specific to their personal characteristics such as age and time since surgery.

The effect of diet-induced insulin resistance on DNA methylation of the androgen receptor promoter in the penile cavernosal smooth muscle of mice.

Population studies have suggested an association between diabetes and the symptoms of testosterone deficiency. Recently, the expression of the androgen receptor (AR) has been shown to be decreased in diabetic patients. Furthermore, diabetes has been shown to induce global methylation. In this study, we used an animal model to investigate whether diabetes results in increased methylation of the AR promoter and whether these changes are associated with the decreased expression of AR in penile cavernosal smooth muscle tissue. Twenty C57BL/6J mice were divided into two groups, receiving either high- (mature diabetic) or low- (mature control) caloric meals for 14 weeks. Another 10 mice were killed at 1 week (young control). Animals in the mature diabetic group showed decreased testosterone levels, although this was not statistically significant. In both control groups, no significant methylation was observed in the AR promoter region CpG island (-85 to +339). In the mature diabetic group, significant methylation was observed at +185 and +200 of the AR promoter. These changes were associated with increased homeostatic model assessment for insulin resistance (HOMA-IR) and decreased corpus cavernosal tissue mass and expression of AR mRNA and protein. We conclude that in these animals, insulin resistance increased the methylation of the GC-rich regions of the AR promoter, leading to decreased AR expression.

Comparative analysis between thoracic spinal cord and sacral neuromodulation in a rat spinal cord injury model: a preliminary report of a rat spinal cord stimulation model.

OBJECTIVE: The purpose of this study is to compare a neuroprotective effect of thoracic cord neuromodulation to that of sacral nerve neuromodulation in rat thoracic spinal cord injury (SCI) model. METHODS: Twenty female Sprague Dawley rats were randomly divided into 4 groups: the normal control group (n=5), SCI with sham stimulation group (SCI, n=5), SCI with electrical stimulation at thoracic spinal cord (SCI + TES, n=5), and SCI with electrical stimulation at sacral nerve (SCI + SES, n=5). Spinal cord was injured by an impactor which dropped from 25mm height. Electrical stimulation was performed by the following protocol: pulse duration, 0.1ms; frequency, 20 Hz; stimulation time, 30 minutes; and stimulation duration at thoracic epidural space and S2 or 3 neural foramina for 4 weeks. Locomotor function, urodynamic study, muscle weights, and fiber cross sectional area (CSA) were investigated. RESULTS: All rats of the SCI + TES group expired within 3 days after the injury. The locomotor function of all survived rats improved over time but there was no significant difference between the SCI and the SCI + SES group. All rats experienced urinary retention after the injury and recovered self-voiding after 3-9 days. Voiding contraction interval was 25.5±7.5 minutes in the SCI group, 16.5±5.3 minutes in the SCI+SES group, and 12.5±4.2 minutes in the control group. The recovery of voiding contraction interval was significant in the SCI + SES group comparing to the SCI group (p<0.05). Muscle weight and CSA were slightly greater in the SCI + SES than in the SCI group, but the difference was not significant. CONCLUSION: We failed to establish a rat spinal cord stimulation model. However, sacral neuromodulation have a therapeutic potential to improve neurogenic bladder and muscle atrophy.

Neuroprotective effects of sacral epidural neuromodulation following spinal cord injury : an experimental study in rats.

OBJECTIVE: The purpose of this study is to evaluate neuroprotective effect of sacral neuromodulation in rat spinal cord injury (SCI) model in the histological and functional aspects. METHODS: Twenty-one female Sprague Dawley rats were randomly divided into 3 groups : the normal control group (CTL, n=7), the SCI with sham stimulation group (SCI, n=7), and the SCI with electrical stimulation (SCI+ES, n=7). Spinal cord was injured by dropping an impactor from 25 mm height. Sacral nerve electrical stimulation was performed by the following protocol : pulse duration, 0.1 ms; frequency, 20 Hz; stimulation time, 30 minutes; and stimulation duration, 4 weeks. Both locomotor function and histological examination were evaluated as scheduled. RESULTS: The number of anterior horn cell was 12.3±5.7 cells/high power field (HPF) in the CTL group, 7.8±4.9 cells/HPF in the SCI group, and 6.9±5.5 cells/HPF in the SCI+ES group, respectively. Both the SCI and the SCI+ES groups showed severe loss of anterior horn cells and myelin fibers compared with the CTL group. Cavitation and demyelinization of the nerve fibers has no significant difference between the SCI group and the SCI+ES group. Cavitation of dorsal column was more evident in only two rats of SCI group than the SCI+ES group. The locomotor function of all rats improved over time but there was no significant difference at any point in time between the SCI and the SCI+ES group. CONCLUSION: In a rat thoracic spinal cord contusion model, we observed that sacral neuromodulation did not prevent SCI-induced myelin loss and apoptosis.

Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis.

Understanding the genetic architecture of cancer pathways that distinguishes subsets of human cancer is critical to developing new therapies that better target tumors based on their molecular expression profiles. In this study, we identify an integrated gene signature from multiple transgenic models of epithelial cancers intrinsic to the functions of the Simian virus 40 T/t-antigens that is associated with the biological behavior and prognosis for several human epithelial tumors. This genetic signature, composed primarily of genes regulating cell replication, proliferation, DNA repair, and apoptosis, is not a general cancer signature. Rather, it is uniquely activated primarily in tumors with aberrant p53, Rb, or BRCA1 expression but not in tumors initiated through the overexpression of myc, ras, her2/neu, or polyoma middle T oncogenes. Importantly, human breast, lung, and prostate tumors expressing this set of genes represent subsets of tumors with the most aggressive phenotype and with poor prognosis. The T/t-antigen signature is highly predictive of human breast cancer prognosis. Because this class of epithelial tumors is generally intractable to currently existing standard therapies, this genetic signature identifies potential targets for novel therapies directed against these lethal forms of cancer. Because these genetic targets have been discovered using mammary, prostate, and lung T/t-antigen mouse cancer models, these models are rationale candidates for use in preclinical testing of therapies focused on these biologically important targets.

Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase.

Recently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable. The efficacy of its antitumor activity largely depends on the level of intracellular ASS, which enables tumor cells to recycle citrulline to arginine. Thus, we examined the expression levels of ASS in various cancer cells and found that it is low in renal cell carcinoma (RCC) cells, rendering the cells highly sensitive to arginine deprivation by ADI treatment. Immunohistochemical analysis revealed that in biopsy specimens from RCC patients (n = 98), the expression of ASS is highly demonstrated in the epithelium of normal proximal tubule but not seen in tumor cells. Furthermore, RCC cells treated with ADI showed remarkable growth retardation in a dose dependent manner. ADI also exerted in vivo antiproliferative effect on the allografted renal cell carcinoma (RENCA) tumor cells and prolonged the survival of tumor-bearing mice. Histological examination of the tumors revealed that tumor angiogenesis and vascular endothelial growth factor (VEGF) expression were significantly diminished by ADI administration. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of RCC in ways of inhibitions of arginine availability and neovascularization.

Prostate cancer and the genomic revolution: Advances using microarray analyses.

The emerging technology of microarray analysis allows the establishment of molecular portraits of prostate cancer and the discovery of novel genes involved in the carcinogenesis process. Many novel genes have already been identified using this technique, and functional analyses of these genes are currently being tested. The combination of microarray analysis with other recently developed high-throughput techniques, such as proteomics, tissue arrays, and gene promoter-methylation, especially using tissue microdissection methods, will provide us with more comprehensive insights into how prostate cancer develops and responds to gene-targeted therapies. Animal models of prostate cancer are being characterized by high throughput techniques to better define the similarities and differences between those models and the human disease, and to determine whether particular models may be useful for specific targeted therapies in pre-clinical studies. Although profiling of mRNA expression provides important information of gene expression, the development of proteomic technologies will allow for an even more precise global insight into cellular signaling and structural alterations during prostate carcinogenesis. Not only will the "omic" revolution change basic science, but it will lead to a new era of molecular medicine.