RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Epigenetic silencing of the RAS association domain family 1A (<it>RASSF1A</it>) tumor suppressor gene promoter has been demonstrated in renal cell carcinoma (RCC) as a result of promoter hypermethylation. Contradictory results have been reported for <it>RASSF1A </it>methylation in normal kidney, thus it is not clear whether a significant difference between <it>RASSF1A </it>methylation in normal and tumor cells of the kidney exists. Moreover, RASSF1A expression has not been characterized in tumors or normal tissue as yet.</p> <p>Results</p> <p>Using combined bisulfite restriction analysis (COBRA) we compared RASSF1A methylation in 90 paired tissue samples obtained from primary kidney tumors and corresponding normal tissue. Bisulfite sequence analysis was carried out using both pooled amplicons from the tumor and normal tissue groups and subclones obtained from a single tissue pair. Expression of RASSF1A was analyzed by the use of tissue arrays and immunohistochemistry. We found significantly increased methylation in tumor samples (mean methylation, 20%) compared to corresponding normal tissues (mean methylation, 11%; <it>P </it>< 0.001). Densely methylated sequences were found both in pooled and individual sequences of normal tissue. Immunohistochemical analysis revealed a significant reduced expression of RASSF1A in most of the tumor samples. Heterogeneous expression patterns of RASSF1A were detected in a subgroup of histologically normal tubular epithelia.</p> <p>Conclusion</p> <p>Our methylation and expression data support the hypothesis that <it>RASSF1A </it>is involved in early tumorigenesis of renal cell carcinoma.</p

Re: Results of a randomized trial of treatment modalities in patients with low or early‑intermediate risk prostate cancer (PREFERE trial)

The authors of this 'Letter to the Editors' express their major concern about selective and biased reporting in this paper

Effects of a 15-Month Supervised Exercise Program on Physical and Psychological Outcomes in Prostate Cancer Patients Following Prostatectomy: The ProRehab Study

Purpose. Despite advanced medical treatment options, many prostate cancer patients are still confronted with unfavorable physical and psychological burdens. Physical exercise has proven to be beneficial for prostate cancer patients, yet specific exercise offers are rare. The ProRehab Study aimed to evaluate the exercise program offered in rehabilitative prostate cancer sports groups in Germany and determine whether it is beneficial for patients following prostatectomy. Methods. Eighty-five prostate cancer patients were recruited for a multicenter, 2-armed, nonrandomized controlled trial 6 to 12 weeks after prostatectomy. The intervention group (n = 56) took part in a 15-month supervised multimodal exercise program. Exercise sessions took place once a week for 60 minutes at a moderate intensity (3.84-4.84 MET-hour). The control group (n = 29) received no intervention. Outcomes included aerobic fitness, activity levels, quality of life, disease- and treatment-related adverse effects, such as urinary incontinence and erectile dysfunction, and relapse-relevant blood values. Intention-to-treat analysis was performed. Results. A significant between-group difference was observed in the urinary symptom score (P = .027). Physical fitness, urinary incontinence, physical, role, emotional, and social functioning, as well as further disease- and treatment-related side effects (dyspnea, urinary, and bowel symptoms) significantly improved within the intervention group. Erectile dysfunction and physical activity levels improved similarly in both groups. Conclusions. The presented data hint at the potential of rehabilitative sports groups for prostate cancer patients. However, according to the current state of the art, exercise intensity and volume may need to be increased to enhance the effects. A number of shorter studies (8-24 weeks) have proven significant between-group differences in quality of life, incontinence, and fitness outcomes when patients exercised 2 to 3 times per week. This is the first exercise intervention study with prostate cancer patients that was conducted over 15 months. Further studies are necessary to investigate whether prostate cancer patients recover sooner when receiving a supervised exercise program