Vitamin D and testosterone co-ordinately modulate intracellular zinc levels and energy metabolism in prostate cancer cells.

Vitamin D3 and its receptor are responsible for controlling energy expenditure in adipocytes and have direct roles in the transcriptional regulation of energy metabolic pathways. This phenomenon also has a significant impact on the etiology of prostate cancer (PCa). Using several in vitro models, the roles of vitamin D3 on energy metabolism and its implication in primary, early, and late invasive PCa were investigated. BODIPY staining and qPCR analyses show that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates de novo lipogenesis in PCa cells by orchestrating transcriptional regulation that affects cholesterol and lipid metabolic pathways. This lipogenic effect is highly dependent on the interaction of several nuclear receptors and their corresponding ligands, including androgen receptor (AR), vitamin D receptor (VDR), and retinoid X receptor (RXR). In contrast, inhibition of peroxisome proliferator-activated receptor alpha (PPARα) signaling blocks the induction of the lipogenic phenotype induced by these receptors. Furthermore, 1,25(OH)2D3, T, and 9 cis-retinoic acid (9-cis RA) together redirect cytosolic citrate metabolism toward fatty acid synthesis by restoring normal prostatic zinc homeostasis that functions to truncate TCA cycle metabolism. 1,25(OH)2D3, T, and 9-cis RA also exert additional control of TCA cycle metabolism by down-regulating SLC25A19, which limits the availability of the co-factor thiamine pyrophosphate (TPP) that is required for enzymatic catalyzation of citrate oxidation. This extensive metabolic reprogramming mediated by 1,25(OH)2D3, T, and 9-cis RA is preserved in all in vitro cell lines investigated. These data suggest that 1,25(OH)2D3 and T are important regulators of normal prostatic energy metabolism. Based on the close association between energy metabolism and cancer progression, supplementation of vitamin D3 and testosterone can restrict the energy production that is required to drive PCa progression by maintaining proper zinc homeostasis and inhibiting TCA cycle activity in PCa cells.

Placebo Medication and Sham Surgery Responses in Benign Prostatic Hyperplasia Treatments: Implications for Clinical Trials.

Placebo medications and sham surgeries have long been thought to be inert treatments. These groups served as a threshold to which an active treatment should be compared in a randomized trial to determine the true efficacy of the active treatment. However, surprising changes in subjective symptom scores and objective measures of voiding have been demonstrated in numerous placebo medication or sham surgery arms of trials. The exact mechanisms by which these inactive treatments augment patient outcomes are not clearly defined and multiple theories have been proposed to explain the often pronounced response. It appears that urologic outcomes are particularly prone to these effects and the astute physician should keep these responses in mind when interpreting any trial on a new therapy.

Assessing resident surgical competency in urology using a global rating scale.

OBJECTIVE: Training programs must ensure residents are competent to practice independently. For surgical fields, this is generally done by the faculty who graduate the residents, but there has been no accepted methodology for this process. DESIGN: As part of a generalized survey, attending physicians performing an operation were asked to assess resident competency to perform the operation independently in an average patient, using a single global question. Residents, in a blinded manner, were asked to answer the same question. SETTING: Urology Residency Program, Albany Medical College, Albany, NY. PARTICIPANTS: Participants included 12 resident physicians and 10 attending physicians. RESULTS: There is a large variation in attending physician assessment of resident surgical competency, and the assessment varies by attending physician and by resident. Generally, attending physicians rated residents lower than the residents rated themselves. The discrepancy was largest for residents early in training and lessened as resident experience increased. Assessments also tended to converge toward the attending physician assessment as competency increased. Assessments had less variability when involving a single, high-volume procedure for a single resident. CONCLUSIONS: Assessing resident surgical competency with a standardized global question is feasible, but complex. Attending physicians and residents differ significantly in their assessment of resident competence. The trend of residents׳ perceptions approaching attending physician estimates as training and competence increases supports the current concept that program directors should use attending physician assessments as the primary measure.