The androgen receptor can signal through Wnt/β-Catenin in prostate cancer cells as an adaptation mechanism to castration levels of androgens

<p>Abstract</p> <p>Background</p> <p>A crucial event in Prostate Cancer progression is the conversion from a hormone-sensitive to a hormone-refractory disease state. Correlating with this transition, androgen receptor (AR) amplification and mutations are often observed in patients failing hormonal ablation therapies. β-Catenin, an essential component of the canonical Wnt signaling pathway, was shown to be a coactivator of the AR signaling in the presence of androgens. However, it is not yet clear what effect the increased levels of the AR could have on the Wnt signaling pathway in these hormone-refractory prostate cells.</p> <p>Results</p> <p>Transient transfections of several human prostate cancer cell lines with the AR and multiple components of the Wnt signaling pathway demonstrate that the AR overexpression can potentiate the transcriptional activities of Wnt/β-Catenin signaling. In addition, the simultaneous activation of the Wnt signaling pathway and overexpression of the AR promote prostate cancer cell growth and transformation at castration levels of androgens. Interestingly, the presence of physiological levels of androgen or other AR agonists inhibits these effects. These observations are consistent with the nuclear co-localization of the AR and β-Catenin shown by immunohistochemistry in human prostate cancer samples. Furthermore, chromatin immunoprecipitation assays showed that Wnt3A can recruit the AR to the promoter regions of Myc and Cyclin D1, which are well-characterized downstream targets of the Wnt signalling pathway. The same assays demonstrated that the AR and β-Catenin can be recruited to the promoter and enhancer regions of a known AR target gene PSA upon Wnt signaling. These results suggest that the AR is promoting Wnt signaling at the chromatin level.</p> <p>Conclusion</p> <p>Our findings suggest that the AR signaling through the Wnt/β-Catenin pathway should be added to the well established functional interactions between both pathways. Moreover, our data show that via this interaction the AR could promote prostate cell malignancy in a ligand-independent manner.</p

Tratamientos Psicológicos Empíricamente Apoyados Para Adultos: Una Revisión Selectiva [Evidence-Based Psychological Treatments for Adults: A Selective Review]

Antecedentes: los tratamientos psicológicos han mostrado su efi cacia, efectividad y efi ciencia para el abordaje de los trastornos mentales; no obstante, considerando el conocimiento científi co generado en los últimos años, no se dispone de trabajos de actualización en español sobre cuáles son los tratamientos psicológicos con respaldo empírico. El objetivo fue realizar una revisión selectiva de los principales tratamientos psicológicos empíricamente apoyados para el abordaje de trastornos mentales en personas adultas. Método: se recogen niveles de evidencia y grados de recomendación en función de los criterios propuestos por el Sistema Nacional de Salud de España (en las Guías de Práctica Clínica) para diferentes trastornos psicológicos. Resultados: los resultados sugieren que los tratamientos psicológicos disponen de apoyo empírico para el abordaje de un amplio elenco de trastornos psicológicos. El grado de apoyo empírico oscila de bajo a alto en función del trastorno psicológico analizado. La revisión sugiere que ciertos campos de intervención necesitan una mayor investigación. Conclusiones: a partir de esta revisión selectiva, los profesionales de la psicología podrán disponer de información rigurosa y actualizada que les permita tomar decisiones informadas a la hora de implementar aquellos procedimientos psicoterapéuticos empíricamente fundamentados en función de las características de las personas que demandan ayuda. // Evidence-Based Psychological Treatments for Adults: A Selective Review. Background: Psychological treatments have shown their effi cacy, effectiveness, and effi ciency in dealing with mental disorders. However, considering the scientifi c knowledge generated in recent years, in the Spanish context, there are no updating studies about empirically supported psychological treatments. The main goal was to carry out a selective review of the main empirically supported psychological treatments for mental disorders in adults. Method: Levels of evidence and degrees of recommendation were collected based on the criteria proposed by the Spanish National Health System (Clinical Practice Guidelines) for different psychological disorders. Results: The results indicate that psychological treatments have empirical support for the approach to a wide range of psychological disorders. These levels of empirical evidence gathered range from low to high depending on the psychological disorder analysed. The review indicates the existence of certain fi elds of intervention that need further investigation. Conclusions: Based on this selective review, psychology professionals will be able to have rigorous, up-to-date information that allows them to make informed decisions when implementing empirically based psychotherapeutic procedures based on the characteristics of the people who require help

Pleurodese nos derrames pleurais malignos: um inquérito entre médicos em países da América do Sul e Central Pleurodesis for malignant pleural effusions: a survey of physicians in South and Central America

OBJETIVO: A pleurodese é uma alternativa eficaz no controle dos derrames pleurais malignos, mas existem controvérsias a respeito de sua indicação e técnica. O objetivo deste estudo foi avaliar como é realizada a pleurodese em países da América do Sul e Central. MÉTODOS: Profissionais que realizam pleurodese responderam um questionário sobre critérios de indicação para pleurodese, técnicas utilizadas e desfechos. RESULTADOS: Nossa amostra envolveu 147 profissionais no Brasil, 49 em outros países da América do Sul e 36 em países da América Central. Mais de 50% dos participantes realizavam pleurodese somente se confirmada a malignidade no derrame pleural. Entretanto, escalas de dispneia e de status de performance eram raramente utilizadas para indicar o procedimento. Aproximadamente 75% dos participantes no Brasil e na América Central preferiam realizar a pleurodese somente no caso de recidiva do derrame, e a expansão pulmonar deveria variar de 90% a 100%. O talco slurry foi o agente mais utilizado, instilado via drenos de calibre intermediário. A toracoscopia foi realizada em menos de 25% dos casos. Febre e dor torácica foram os efeitos adversos mais comuns, e empiema ocorreu em < 14% dos casos. A média de sobrevida após o procedimento variou entre 6 e 12 meses. CONCLUSÕES: Há variações consideráveis quanto aos critérios de indicação para pleurodese, técnicas utilizadas e desfechos entre os países. Talco slurry é o agente mais frequentemente utilizado, e a toracoscopia é a primeira escolha no Brasil. Os baixos índices de complicações e o tempo de sobrevida elevado indicam que a pleurodese é efetiva e causa poucos efeitos adversos.<br>OBJECTIVE: Pleurodesis is an effective alternative for the control of malignant pleural effusions. However, there is as yet no consensus regarding the indications for the procedure and the techniques employed therein. The objective of this study was to evaluate how pleurodesis is performed in South and Central America. METHODS: Professionals who perform pleurodesis completed a questionnaire regarding the indications for the procedure, the techniques used therein, and the outcomes obtained. RESULTS: Our sample comprised 147 respondents in Brazil, 49 in other South American countries, and 36 in Central America. More than 50% of the respondents reported performing pleurodesis only if pleural malignancy had been confirmed. However, scores on dyspnea and performance status scales were rarely used as indications for the procedure. Nearly 75% of the respondents in Brazil and in Central America preferred to perform pleurodesis only for recurrent effusions and stated that lung expansion should be 90-100%. Talc slurry, instilled via medium-sized chest tubes, was the agent most often employed. Thoracoscopy was performed in less than 25% of cases. Fever and chest pain were the most common side effects, and empyema occurred in < 14% of cases. The mean survival time after the procedure was most often reported to be 6-12 months. CONCLUSIONS: There was considerable variation among the countries evaluated in terms of the indications for pleurodesis, techniques used, and outcomes. Talc slurry is the agent most commonly used, and thoracoscopy is the technique of choice in Brazil. Pleurodesis is an effective procedure that has few side effects, as evidenced by the low complication rates and high survival times