BackgroundInsertional mutagenesis screens have been used with great success to identify oncogenes and tumor suppressor genes. Typically, these screens use gammaretroviruses (γRV) or transposons as insertional mutagens. However, insertional mutations from replication-competent γRVs or transposons that occur later during oncogenesis can produce passenger mutations that do not drive cancer progression. Here, we utilized a replication-incompetent lentiviral vector (LV) to perform an insertional mutagenesis screen to identify genes in the progression to androgen-independent prostate cancer (AIPC).MethodsProstate cancer cells were mutagenized with a LV to enrich for clones with a selective advantage in an androgen-deficient environment provided by a dysregulated gene(s) near the vector integration site. We performed our screen using an in vitro AIPC model and also an in vivo xenotransplant model for AIPC. Our approach identified proviral integration sites utilizing a shuttle vector that allows for rapid rescue of plasmids in E. coli that contain LV long terminal repeat (LTR)-chromosome junctions. This shuttle vector approach does not require PCR amplification and has several advantages over PCR-based techniques.ResultsProviral integrations were enriched near prostate cancer susceptibility loci in cells grown in androgen-deficient medium (p < 0.001), and five candidate genes that influence AIPC were identified; ATPAF1, GCOM1, MEX3D, PTRF, and TRPM4. Additionally, we showed that RNAi knockdown of ATPAF1 significantly reduces growth (p < 0.05) in androgen-deficient conditions.ConclusionsOur approach has proven effective for use in PCa, identifying a known prostate cancer gene, PTRF, and also several genes not previously associated with prostate cancer. The replication-incompetent shuttle vector approach has broad potential applications for cancer gene discovery, and for interrogating diverse biological and disease processes.

PURPOSE: Our primary aim was to evaluate the effects of a formalized wellness curriculum on the rate of burnout among University of New Mexico (UNM) obstetrics and gynecology (OBGyn) residents. Our secondary aim was to evaluate the effect of a wellness curriculum on rates of depression, alcohol abuse and suicide risk. BACKGROUND: Burnout is a pathological syndrome characterized by depersonalization, emotional exhaustion and a low sense of personal achievement. Burnout is a concern for resident physicians due to their heavy workload and low sense of autonomy. METHODS: A structured wellness curriculum was instituted at the start of the 2016 academic year. A 45-item survey, consisting of the Maslach Burnout Inventory Human Services Survey (MBI-HSS), personal health questionnaire-9 (PHQ9), suicide behaviors questionnaire-revised (SBQr), and the alcohol use disorders identification test (AUDIT), was to be administered at the start, midpoint, and end of the academic year. RESULTS: The study included 23 UNM OBGyn residents. Midpoint and end of curriculum surveys were collected as planned and demonstrated no difference in rate of burnout. Upon completion of the 2016 academic year 18 (78.2%) residents reported moderate to severe emotional exhaustion; 13 (59.1%) moderate to severe depersonalization; and 5 (21.7%) low personal achievement. SBQ-R identified 4 (18.2%) residents at high risk for suicide and AUDIT-C identified 15 (68.2%) at high risk for alcohol abuse. DISCUSSION: High rates of burnout, depression, alcohol abuse, and suicide risk did not change between the midpoint and end of a structured wellness curriculum.

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However, due to the tumor's indolent nature and a low index of clinical suspicion by physicians, patients often present with locally advanced neoplasms which is unresectable at the time of diagnosis. Patients presenting with ACC are sometimes less than ideal surgical candidates and even when they undergo