RESUMO
BACKGROUND: Treatment of prostate cancer (PCa) may be improved by identifying biological mechanisms of tumor growth that directly impact clinical disease progression. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor phenotype impact PCa biology and recurrence. METHODS: Radical prostatectomy (RP) specimens (±disease recurrence, N = 276) were analyzed by qRT-PCR to quantify expression of genes associated with self-renewal, drug resistance, and tumorigenicity in prior studies. Associations between gene expression and PCa recurrence were confirmed by bootstrap internal validation and by external validation in independent cohorts (total N = 675) and in silico. siRNA knockdown and lentiviral overexpression were used to determine the effect of gene expression on PCa invasion, proliferation, and tumor growth. RESULTS: Four candidate genes were differentially expressed in PCa recurrence. Of these, low AXIN2 expression was internally validated in the discovery cohort. Validation in external cohorts and in silico demonstrated that low AXIN2 was independently associated with more aggressive PCa, biochemical recurrence, and metastasis-free survival after RP. Functionally, siRNA-mediated depletion of AXIN2 significantly increased invasiveness, proliferation, and tumor growth. Conversely, ectopic overexpression of AXIN2 significantly reduced invasiveness, proliferation, and tumor growth. CONCLUSIONS: Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts, and its expression levels in PCa cells significantly impacted invasiveness, proliferation, and tumor growth. Given these novel roles, further study of AXIN2 in PCa may yield promising new predictive and therapeutic strategies.
Assuntos
Proteína Axina , Próstata , Prostatectomia/métodos , Neoplasias da Próstata , Idoso , Proteína Axina/análise , Proteína Axina/genética , Biomarcadores , Humanos , Masculino , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Medição de RiscoRESUMO
OBJECTIVE: To identify factors and stress coping mechanisms associated with burnout within the field of urology. METHODS: A survey study was completed using the abbreviated Maslach Burnout Inventory to evaluate emotional exhaustion, depersonalization, and low personal achievement. Demographic information, training status, practice setting, work hours, and mechanisms used to cope with stress were evaluated. Participants were also asked to comment on contributors to burnout in an open-ended question. Univariate analysis and multivariate regression identified factors associated with measures of burnout. RESULTS: A total of 476 survey responses from 377 practicing urologists and 99 residents/fellows were included. Burnout was identified in 49.6% of all participants. Burnout through high emotional exhaustion was seen in 40.7%, high depersonalization in 30.7%, and low personal achievement in 18.3%. Trainees exhibited higher levels of depersonalization and lower levels of personal achievement. Higher levels of emotional exhaustion were identified in urologists in the middle of their careers and those in private practice. Urologists identified documentation, insurance and reimbursement, government regulations, medical practice expectations, and patient expectations as stressors contributing to burnout. Exercising and socializing were consistently associated with lower measures of burnout whereas stress eating and alcohol use were associated with higher measures of burnout on multivariate analysis. CONCLUSION: Burnout in urology was associated with trainee status, years in practice, and practice setting. Exercising and socializing were protective against burnout whereas stress eating and alcohol consumption were associated with higher rates of burnout.
Assuntos
Adaptação Psicológica , Esgotamento Profissional/psicologia , Internato e Residência , Estresse Psicológico/psicologia , Urologistas/psicologia , Urologia , Logro , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/etiologia , Esgotamento Profissional/prevenção & controle , Despersonalização/epidemiologia , Despersonalização/psicologia , Ingestão de Alimentos/psicologia , Exercício Físico/psicologia , Feminino , Humanos , Internato e Residência/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Motivação , Administração da Prática Médica , Prática Privada , Análise de Regressão , Participação Social/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controle , Inquéritos e Questionários , Urologistas/estatística & dados numéricos , Urologia/estatística & dados numéricos , Adulto JovemRESUMO
Central nervous system (CNS) manifestations of Echinococcus and Schistosoma infections occur throughout the world, with incidence increasing in developed regions. A detailed literature review generated a current summary on epidemiology, parasitology, pathology, clinical manifestations, imaging studies, diagnosis, and treatment of neuroechinococcosis and neuroschistosomiasis. Recent advancements have been made in diagnosis, treatment, and prevention of these parasitic CNS infections. Ongoing advancements in neuroimaging and diagnostic studies, as well as efforts to better understand the parasite genome and host-parasite relationships, will likely continue to improve patient management.