IntroductionProstate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer death among men in the US. The most common site of prostate cancer metastasis is the bone, with up to 84% of patients demonstrating skeletal metastases (1). While initially thought to be primarily osteoblastic, it is now recognized that prostate cancer skeletal metastases have an extensive bone resorptive component (2, 3) that is caused primarily by osteoclasts (4). This accounts, in part, for the ability of bisphosphonates, which are antiosteoclastogenic agents, to diminish osteolysis, decrease pain, and improve mobility in patients with prostate cancer skeletal metastasis (5). However, the mechanisms through which prostate cancer skeletal metastases induce osteolytic lesions are not defined.The presence of an osteolytic component in prostate cancer skeletal metastases suggests that osteoclastogenesis may play a role in the establishment of these lesions. Recently, the discovery and characterization of a novel cytokine system -the TNF family member, receptor activator of NF-κB ligand (RANKL, also called OPGL, TRANCE, and ODF); its receptor, receptor activator of NF-κB (RANK, also called ODAR); and its decoy receptor, osteoprotegerin (OPG, also called OCIF and TR1) -has established a common mechanism through which osteoclastogenesis is regulated in normal bone (reviewed in ref. 6). RANKL, a transmembrane molecule located on bone marrow stromal cells and osteoblasts, binds to RANK, which is located on the surface of osteoclast precursors. This ligand-receptor interaction activates NF-κB, which stimulates differentiation of osteoclast precursors to osteoclasts. OPG, also produced by osteoblasts/stromal cells, binds to RANKL, sequestering it from binding to RANK, which results in inhibition of osteoclastogenesis. The requirement for RANKL to induce osteoclastogenesis suggests that it may mediate the osteolytic component of prostate cancer skeletal lesions. However, it is currently unknown if prostate cancer uses the Prostate cancer (CaP) forms osteoblastic skeletal metastases with an underlying osteoclastic component. However, the importance of osteoclastogenesis in the development of CaP skeletal lesions is unknown. In the present study, we demonstrate that CaP cells directly induce osteoclastogenesis from osteoclast precursors in the absence of underlying stroma in vitro. CaP cells produced a soluble form of receptor activator of NF-κB ligand (RANKL), which accounted for the CaP-mediated osteoclastogenesis. To evaluate for the importance of osteoclastogenesis on CaP tumor development in vivo, CaP cells were injected both intratibially and subcutaneously in the same mice, followed by administration of the decoy receptor for RANKL, osteoprotegerin (OPG). OPG completely prevented the establishment of mixed osteolytic/osteoblastic tibial tumors, as were observed in vehicle-treated animals, but it had no effect on subcutaneous tumor growth. Consistent with the role of osteoclasts in tumor development, oste...

BACKGROUND Drug use (illicit drug use and nonmedical use of prescription drugs) is common but under-recognized in primary care settings. We validated a single-question screening test for drug use and drug use disorders in primary care. METHODS Adult patients recruited from primary care waiting rooms were asked the single screening question, “How many times in the past year have you used an illegal drug or used a prescription medication for non-medical reasons?” A response of ≥1 was considered positive. They were also asked the 10-item Drug Abuse Screening Test (DAST). The reference standard was the presence or absence of current (past year) drug use or a drug use disorder (abuse or dependence) as determined by a standardized diagnostic interview. Drug use was also determined by oral fluid testing for common drugs of abuse. RESULTS Of 394 eligible primary care patients, 286 (73%) completed the interview. The single screening question was 100% sensitive (95% CI 90.6% to 100%) and 73.5% specific (95% CI 67.7% to 78.6%) for the detection of a drug use disorder. It was less sensitive for the detection of self-reported current drug use (92.9%, 95% CI 86.1% to 96.5%) and drug use detected by oral fluid testing or self-report (81.8%, 95% CI 72.5% to 88.5%). Test characteristics were similar to that of the DAST, and were affected very little by subject demographic characteristics. CONCLUSIONS The single screening question accurately identified drug use in this sample of primary care patients, supporting the utility of this brief screen in primary care.

BACKGROUNDUnhealthy alcohol use is prevalent but under-diagnosed in primary care settings.OBJECTIVETo validate, in primary care, a single-item screening test for unhealthy alcohol use recommended by the National Institute on Alcohol Abuse and Alcoholism (NIAAA).DESIGNCross-sectional study.PARTICIPANTSAdult English-speaking patients recruited from primary care waiting rooms.MEASUREMENTSParticipants were asked the single screening question, “How many times in the past year have you had X or more drinks in a day?”, where X is 5 for men and 4 for women, and a response of >1 is considered positive. Unhealthy alcohol use was defined as the presence of an alcohol use disorder, as determined by a standardized diagnostic interview, or risky consumption, as determined using a validated 30-day calendar method.MAIN RESULTSOf 394 eligible primary care patients, 286 (73%) completed the interview. The single-question screen was 81.8% sensitive (95% confidence interval (CI) 72.5% to 88.5%) and 79.3% specific (95% CI 73.1% to 84.4%) for the detection of unhealthy alcohol use. It was slightly more sensitive (87.9%, 95% CI 72.7% to 95.2%) but was less specific (66.8%, 95% CI 60.8% to 72.3%) for the detection of a current alcohol use disorder. Test characteristics were similar to that of a commonly used three-item screen, and were affected very little by subject demographic characteristics.CONCLUSIONSThe single screening question recommended by the NIAAA accurately identified unhealthy alcohol use in this sample of primary care patients. These findings support the use of this brief screen in primary care.

RKIP does not influence the tumorigenic properties of human prostate cancer cells. It appears to be a novel and clinically relevant suppressor of metastasis that may function by decreasing vascular invasion.