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Despite recent insights into prostate cancer (PCa)-associated genetic changes, full understanding of prostate tumorigenesis remains elusive owing to complexity of interactions among various cell types and soluble factors present in prostate tissue. We found the upregulation of nuclear factor of activated T cells c1 (NFATc1) in human PCa and cultured PCa cells, but not in normal prostates and non-tumorigenic prostate cells. To understand the role of NFATc1 in prostate tumorigenesis in situ, we temporally and spatially controlled the activation of NFATc1 in mouse prostate and showed that such activation resulted in prostatic adenocarcinoma with features similar to those seen in human PCa. Our results indicate that the activation of a single transcription factor, NFATc1 in prostatic luminal epithelium to PCa can affect expression of diverse factors in both cells harboring the genetic changes and in neighboring cells through microenvironmental alterations. In addition to the activation of oncogenes c-MYC and STAT3 in tumor cells, a number of cytokines and growth factors, such as IL1β, IL6 and SPP1 (osteopontin, a key biomarker for PCa), were upregulated in NFATc1-induced PCa, establishing a tumorigenic microenvironment involving both NFATc1 positive and negative cells for prostate tumorigenesis. To further characterize interactions between genes involved in prostate tumorigenesis, we generated mice with both NFATc1 activation and Pten inactivation in prostate. We showed that NFATc1 activation led to acceleration of Pten null-driven prostate tumorigenesis by overcoming the PTEN loss-induced cellular senescence through inhibition of p21 activation. This study provides direct in vivo evidence of an oncogenic role of NFATc1 in prostate tumorigenesis and reveals multiple functions of NFATc1 in activating oncogenes, in inducing proinflammatory cytokines, in oncogene addiction, and in overcoming cellular senescence, which suggests calcineurin-NFAT signaling as a potential target in preventing PCa., Competing Interests: The authors declare no conflict of interest.

Stereotactic radiosurgery and percutaneous radiofrequency ablation are emerging therapies for pain palliation and local control of spinal metastases. However, the post-treatment imaging findings are not well characterized and the risk of long-term complications is unknown. We present the case of a 46-year-old woman with delayed vertebral body collapse after stereotactic radiosurgery and radiofrequency ablation of a painful lumbar metastasis. Histopathologic-MRI correlation confirmed osteonecrosis as the underlying etiology and demonstrated that treatment-induced vascular fibrosis and tumor progression can have identical imaging appearances., (© The Author(s) 2015.)

The OnControl coaxial biopsy system (Vidacare Corporation, Shavano Park, TX) includes an inner diamond-tipped access needle and hollow biopsy needle that engage with a battery-powered hand drill. Herein, we report the use of this novel device to perform two CT-guided percutaneous skull biopsies. Both procedures were performed without complication and facilitated a pathologic diagnosis., (© The Author(s) 2015.)

Purpose: Evidence shows acanthosis nigricans is often associated with hyperinsulinemia and may indicate increased risk of type 2 diabetes mellitus. The purpose of this study was to determine the association of acanthosis nigricans with type 2 diabetes risk factors and disease in young persons., Methods: We conducted a cross-sectional study in the Research in Outpatient Settings Network, a practice-based research network in southwestern US communities. Participating clinicians (N = 96) collected data on children and young adults aged 7 to 39 years seen during a 2-week sampling period. The main outcomes were the prevalence of acanthosis nigricans, type 2 diabetes risk factors (ethnicity, family history of type 2 diabetes, hypertension, overweight/obesity), type 2 diabetes, and the relationships among these., Results: Among 1,133 patients sampled, risk factors for type 2 diabetes were common: 69% had a family history of the disease; 3% of children (aged 7 to 19 years) and 12% of adults had hypertension; 43% of children and 73% of adults were overweight or obese; and 80% were members of ethnic minorities. Acanthosis nigricans was found in 17% of children and 21% of adults. Among children and adults alike, the more type 2 diabetes risk factors that were present, the higher the prevalence of acanthosis nigricans (P <.001). The prevalence ratio for type 2 diabetes in patients with acanthosis nigricans was 1.97 (95% confidence interval, 1.18-3.27; P = .01) after controlling for age, body mass index, and the number of type 2 diabetes risk factors. Clinicians reported that the identification of acanthosis nigricans frequently led to discussions about lifestyle modification for decreasing the risk of type 2 diabetes., Conclusions: Patients with acanthosis nigricans are likely to have multiple risk factors for type 2 diabetes. Acanthosis nigricans may be an independent risk factor for this disease. Detection of acanthosis nigricans may help clinicians more rapidly identify high-risk individuals for diabetes counseling.