Combined Analysis of Biparametric MRI and Prostate-Specific Antigen Density: Role in the Prebiopsy Diagnosis of Gleason Score 7 or Greater Prostate Cancer.

OBJECTIVE: The objective of our study was to investigate the diagnostic performance of prebiopsy biparametric MRI (bpMRI) and prostate-specific antigen density (PSAD) for Gleason score (GS) 7 or greater prostate cancer (PCa). MATERIALS AND METHODS: Sixty-eight consecutive patients who underwent prebiopsy bpMRI and biopsy were included. Pathologic results of systemic and targeted biopsies were the reference standard. Qualitative analyses comprised Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and modified PI-RADSv2 (mPI-RADSv2). Quantitative analyses comprised mean apparent diffusion coefficient (ADC) of tumor, 10th percentile ADC of tumor, mean ADC ratio (ADCR) between benign tissues and PCa, and 10th percentile ADCR between benign tissues and PCa. The AUCs of the following combined models for GS 7 or greater PCa were investigated: model 1, PSAD and PI-RADSv2; model 2, PSAD and mPI-RADSv2; model 3, PSAD and mean ADC; model 4, PSAD and 10th percentile ADC; model 5, PSAD and mean ADCR; and model 6, PSAD and 10th percentile ADCR. RESULTS: The rate of GS 7 or greater PCa was 45.6% (31/68). AUCs of bpMRI parameters were 0.816 for PI-RADSv2, 0.838 for mPI-RADSv2, 0.820 for mean ADC, 0.823 for 10th percentile ADC, 0.780 for mean ADCR, and 0.763 for 10th percentile ADCR (p > 0.05 in all comparisons), whereas AUCs of prostate-specific antigen (PSA)-based parameters were 0.650 for PSA and 0.745 for PSAD (PSA vs PSAD, p = 0.017). AUCs of the combined models from 1 to 6 were 0.860, 0.880, 0.837, 0.844, 0.811, and 0.806, respectively, for biopsy GS 7 or greater PCa (p > 0.05 in all comparisons). CONCLUSION: Combined analysis of prebiopsy bpMRI and PSAD is useful for identifying GS 7 or greater PCa.

Somatotroph-Specific Aip-Deficient Mice Display Pretumorigenic Alterations in Cell-Cycle Signaling.

Patients with familial isolated pituitary adenoma are predisposed to pituitary adenomas, which in a subset of cases is due to germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Using Cre/lox and Flp/Frt technology, a conditional mouse model was generated to examine the loss of the mouse homolog, Aip, in pituitary somatotrophs. By 40 weeks of age, >80% of somatotroph specific Aip knockout mice develop growth hormone (GH) secreting adenomas. The formation of adenomas results in physiologic effects recapitulating the human syndrome of acromegaly, including increased body size, elevated serum GH and insulin-like growth factor 1 levels, and glucose intolerance. The pretumorigenic Aip-deficient somatotrophs secrete excess GH and exhibit pathologic hyperplasia associated with cytosolic compartmentalization of the cyclin-dependent kinase (CDK) inhibitor p27kip1 and perinuclear accentuation of CDK-4. Following tumor formation, the Aip-deficient somatotrophs display reduced expression of somatostatin receptor subtype 5 with impaired response to octreotide. The delayed tumor emergence, even with loss of both copies of Aip, implies that additional somatic events are required for adenoma formation. These findings suggest that pituitary hyperplasia precedes adenomatous transformation in somatotroph-specific Aip-deficient mice and reveal potential mechanisms involved in the pretumorigenic state that ultimately contribute to transformation.

The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes.

BACKGROUND: Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes. METHODS: For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments. RESULTS: RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group. CONCLUSION: RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.