Tumor-initiating subpopulations of cancer cells, also known as cancer stem cells (CSCs), were recently identified and characterized in Prostate cancer (PCa). We theorized that the PI3K/AKT pathway ...and mTOR, one of its main effectors, play a role in CSC maintenance. Moreover, hypoxia was known to be involved in CSC maintenance and to have a regulating effect on mTOR signaling.
In our study, we therefore evaluated the effects of mTOR inhibitors on proliferation, assessed the activity of the mTOR pathway and measured the mitochondrial activity as well as levels of radical oxygen species (ROS) of human as well as murine CSCs in vitro. Further, we examined basal levels of mediators of hypoxic signaling such as HIF1α and its effectors.We isolated CSC like cells from the human PCa cell line DU145 and the murine PCa cell line TRAMPC1 using FACS according to their expression of the stem cell markers CD44, CD49f and Sca-1. We used sphere formation assays to confirm stem and progenitor cell properties. Next, we treated the CSC and non-CSC cell populations with mTOR inhibitors under normoxic and hypoxic conditions in order to determine their cell viability at time points up to 72h. Mitochondrial activity was measured using extracellular flux (XF) analysis and levels of ROS were obtained using ROS-specific fluorescent dyes and flow cytometry. Our results suggest that CSC like PCa cells are more resistant to mTOR inhibitors when compared to their non-CSC counterparts. Most interestingly, while the non-CSC population displays higher sensitivity to mTOR inhibitors under hypoxic conditions, the viability of CSCs remains unaffected. Immunoblotting uncovers generally lower mTOR activity in CSCs compared to non-CSCs. Hypoxia leads to a decrease in mTOR activity in both subpopulations, though this effect is stronger in CSC like subpopulations through higher HIF1α-mediated negative feedback in both cell lines studied. At the same time we do not observe alterations in signaling through AR or PI3K downstream effectors besides mTOR, such as AKT. We propose that prostate CSCs might be resistant against mTOR inhibition and that inhibitors targeting multiple kinases along the PI3K/AKT/mTOR axis would be more effective. Our findings could be helpful to assess the impact of mTOR targeted therapy in prostate cancer in light of ongoing clinical trials.
All authors have declared no conflicts of interest.
ABSTRACT There are currently various concepts related to quality, which have been implemented by many hospitals and other healthcare institutions. The search for continuous improvement, the ...implementation of a quality culture and hospital accreditation have also been common, in these institutions. However, the history of hospital audits and accreditation is complex and full of dynamic concepts. The American College of Surgeons was pioneer in publishing, more than a century ago, the first document pertaining quality standards. After that, various programs and concepts have been developed and remodeled by distinct entities. In this article, we briefly review the history of quality in the world and Brazil. We also discuss related concepts regarding its assessment in healthcare.
RESUMO Sólidos conceitos de qualidade assistencial são adotados em grandes hospitais e serviços de saúde da atualidade. A busca por melhoria contínua, implementação de cultura de qualidade e obtenção de selos de certificação em qualidade hospitalar é comum em tais instituições. Entretanto, a história da avaliação hospitalar e do processo de certificação é longa e repleta de conceitos dinâmicos. O “American College of Surgeons” foi pioneiro ao publicar há mais de um século o primeiro documento contendo diretrizes sobre padrões de qualidade a serem seguidos. Posteriormente, múltiplos programas e conceitos foram criados e remodelados por distintas entidades. Neste artigo, apresentamos breve revisão da história da qualidade no mundo e no Brasil, além de alguns conceitos relacionados à avaliação da mesma em saúde.
Prostate cancer is the most prevalent cancer in males in developed countries. Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though ...its function has not been characterized. TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular.
ABSTRACT Objective: to compare intraperitoneal adhesion formation in rats when using polypropylene and polypropylene with poliglecaprone meshes. Methods: we used twenty male, Wistar rats, divided in ...two groups. In group 1, the rats received the polypropylene mesh on their right side and the polypropylene with poliglecaprone mesh on their left side. In group 2 the position of the meshes was inverted. After 30 days, we analyzed the presence or not of adhesion formation, including only those over the meshes. The findings undergone an analysis through the Mann-Whitney test, at a level of significance of p≤0.05. Results: all meshes presented adhesions. We verified that, for the polypropylene meshes, the percentage of their surface covered by adhesions varied from 10.5 to 100%, with an average of 34.07±24.21%, while for the polypropylene with poliglecaprone mesh, the percentage covered by adhesions varied between 8.5% and 100%, with an average of 44.7±32.85% (p=0.12). Conclusion: both meshes lead to adhesion formation, none being superior to the other.
RESUMO Objetivo: comparar a formação de aderências intraperitoneais em ratos, com o uso de tela de polipropileno e tela composta de polipropileno e poliglecaprone. Métodos: vinte ratos Wistar machos, foram alocados em dois grupos. No grupo 1 os ratos receberam tela de polipropileno no lado direito e tela de polipropileno e poliglecaprone no lado esquerdo. No grupo 2 inverteu-se a posição das telas. Analisou-se a presença ou não de aderências após 30 dias, sendo incluídas apenas aderências sobre as telas. Os resultados foram submetidos à análise estatística, adotando-se como nível de significância p≤0,05. Resultados: todas as telas se apresentaram com aderências. Verificou-se que, na tela de polipropileno, a porcentagem de superfície coberta por aderências variou entre 10,5 a 100%, com média 34,07±24,21% enquanto que na tela de polipropileno e poliglecaprone a porcentagem de tela coberta por aderências variou entre 8,5 a 100%, com média 44,7±32,85% (p=0,12) . Conclusão: ambas as telas dão origem às aderências, não havendo vantagem de aplicação no reparo intraperitoneal de uma em relação à outra.
RESUMO Objetivo: avaliar a percepção dos cirurgiões, membros do Colégio Brasileiro de Cirurgiões (CBC), sobre temas de segurança e qualidade em cirurgia, com base em Projetos do Ministério da Saúde ...(MS), do CBC, da Organização Mundial de Saúde (OMS) e do Colégio Americano de Cirurgiões (ACS). Métodos: questionário com base nas iniciativas da OMS, do CBC e do ACS foi enviado pelo Survey Monkey a todos os sócios, ativos e não ativos, do CBC em março de 2018. Resultados: responderam ao questionário 171 profissionais dentre os 7.100 sócios. Desses, a maioria (63,2%) declarou praticar Cirurgia Geral, 88,9% indicaram conhecer o Projeto Cirurgia Segura do MS, 73,1%, o Manual do CBC e 14,6%, o Strong for Surgery do ACS. Entre os que conhecem o Projeto do MS, 73,1% disseram usá-lo como rotina e, entre os que conhecem o Manual do CBC, 46,2% usam-no. A maior parte dos cirurgiões (81,3%) indicou que já vivenciou falha cirúrgica grave, sendo aquelas relacionadas com material cirúrgico (49,7%) e presença de corpos estranhos (8,2%), isoladamente, as mais comuns. Houve opiniões distintas sobre a responsabilidade de conferência do checklist. Conclusão: a importância da segurança e qualidade em cirurgia é conhecida pelos cirurgiões, mas a prática é variada. Eventos adversos graves foram vivenciados por muitos cirurgiões, principalmente relacionados com material cirúrgico e corpos estranhos. O conceito de interdisciplinaridade parece não ser prática comum. Os dados indicam a necessidade de desenvolver projetos de educação e a obrigatoriedade de auditorias.
ABSTRACT Objective: to evaluate the perception of surgeons, members of the Brazilian College of Surgeons (CBC), on safety and quality issues in surgery, based on projects of Brazilian Ministry of Health (MS), CBC, World Health Organization (WHO), and American College of Surgeons (ACS). Methods: a questionnaire based on WHO, CBC, and ACS initiatives was sent to all active and non-active CBC members, using Survey Monkey, in March 2018. Results: out of 7,100 members, 171 professionals answered the questionnaire. Out of these, the majority (63.2%) declared to perform general surgery, 88.9% indicated knowing the project called Safe Surgery developed by MS, 73.1%, the CBC manual, and 14.6%, the ACS Strong for Surgery. Among those who indicated knowing the MS project, 73.1% said that they were accustomed to use it as a routine, and, among those who indicated knowing the CBC manual, 46.2% said that they were accustomed to use it. Most of the surgeons (81.3%) indicated that they had experienced severe surgical failures, being failures related to surgical material (49.7%) and presence of foreign bodies (8.2%) the most common ones. There were distinct opinions on who was responsible for checking over the checklist. Conclusion: the importance of safety and quality in surgery is well known by surgeons, but the practice is varied. Serious adverse events had been experienced by many surgeons, mainly related to surgical material and foreign bodies. The concept of interdisciplinarity did not seem to be common practice. Data indicated the need to develop education projects and the obligation of audits.
RESUMO Objetivo: avaliar a percepção de qualidade de vida entre residentes no primeiro ano de Residência Médica em relação aos residentes de outros anos, dada a importância dessa questão na saúde. ...Métodos: estudo comparativo, transversal e analítico realizado no período de fevereiro a abril de 2016, realizado em um hospital de trauma terciário de referência do Brasil. Médicos residentes foram submetidos voluntariamente ao questionário validado da Organização Mundial de Saúde (OMS) sobre qualidade de vida, o WHOQOL-BREF, com preenchimento online. Os residentes foram divididos em dois grupos: primeiro ano de residência (R1) e outros anos de residência. Resultados: noventa e sete residentes de diversas especialidades médicas responderam ao questionário. Desses, 59 eram homens e 38, mulheres. A média de idade foi de 27,7 anos. Residentes do primeiro ano representaram 49,5% dos entrevistados. A qualidade de vida de maneira global foi considerada regular em ambos os grupos. Em relação ao domínio psicológico, houve diferença significativa entre o R1 (este, com piores escores neste domínio) e os demais anos de residência (p<0,0000001). Conclusão: a qualidade de vida dos residentes do primeiro ano é pior em relação aos demais, tendo uma variação significativa de sentimento positivo, capacidade de aprender, memória, pensamento e concentração, autoestima, imagem corporal e aparência e sentimentos negativos em relação aos médicos residentes dos outros anos.
ABSTRACT Objective: to evaluate the perception of quality of life among residents in the first year of Medical Residency compared to the one among residents in other years of training, given the importance of this issue in health. Methods: a comparative and cross-sectional analytical study performed from February to April 2016 in a reference tertiary trauma hospital in Brazil. Resident physicians were voluntarily submitted to an online questionnaire on quality of life (called WHOQOL-BREF), validated by World Health Organization (WHO). They were divided into two groups: first year of residency (R1) and other years of residency. Results: ninety-seven residents of several medical specialties answered the questionnaire. Of these, 59 were men and 38 were women. The mean age was 27.7 years. First-year residents accounted for 49.5% of the interviewees. Overall, quality of life was considered regular in both groups. In relation to psychological domain, there was a significant difference between the R1 group (with worse scores in this domain) and the non-R1 group (p<0.0000001). Conclusion: first-year residents’ quality of life is worse than the one of the residents from other years, having a significant variation of positive feelings, learning capacity, memory, thought and concentration, self-esteem, body image and appearance, and negative feelings.
RESUMO Objetivo: avaliar a viabilidade de abreviação do jejum em cirurgias colorretais oncológicas, bem como, o impacto no desfecho cirúrgico dos pacientes. Métodos: estudo prospectivo comparativo ...randomizado com pacientes submetidos à cirurgias eletivas colorretais, por câncer, no período de maio a setembro de 2017. Os pacientes foram randomizados eletronicamente em dois grupos de acordo com o jejum pré-operatório a ser adotado: convencional ou abreviado. Resultados: dos 33 pacientes incluídos, 15 seguiram o protocolo de jejum abreviado e 18 de jejum convencional. Ambos os grupos apresentaram perfis comparáveis. Nenhum paciente foi submetido a preparo mecânico do cólon. Em 69,7% dos casos, a cirurgia envolveu dissecção baixa do reto. Os procedimentos foram equivalentes em relação às variáveis intraoperatórias e complicações graves. O tempo para atingir realimentação plena foi menor para o jejum abreviado (10 versus 16 dias, p=0,001), assim como, o tempo de internação hospitalar (2 versus 4 dias, p=0,009). Os custos hospitalares foram menores no jejum abreviado (331 versus 682 reais, p<0,001). A análise univariável revelou correlação entre a realimentação plena e o jejum abreviado HR 0,29 (IC95%: 0,12-0,68 e com a distensão abdominal HR 0,12(IC95%: 0,01-0,94). Após análise multivariável, o jejum abreviado apresentou menor tempo para realimentação plena HR 0,39(IC95%: 0,16-0,92. Conclusão: o jejum pré-operatório abreviado favorece a recuperação metabólico-nutricional, diminuindo o tempo para realimentação plena. A implantação do protocolo de abreviação do jejum reduz custos de internação hospitalar.
ABSTRACT Objective: to evaluate the feasibility of abbreviated fasting in oncologic colorectal surgeries, as well as the impact on the surgical outcome of the patients. Methods: prospective randomized comparative study with patients undergoing elective colorectal cancer surgeries from May to September 2017. Patients were randomized electronically into two groups according to the preoperative fast to be adopted: conventional or abbreviated. Results: of the 33 patients included, 15 followed the abbreviated fasting protocol and 18 the conventional fasting. Both groups had comparable profiles. No patient underwent mechanical preparation of the colon. In 69.7% of the cases, surgery involved low rectal dissection. The procedures were equivalent in relation to intraoperative variables and severe complications. The time to achieve complete oral intake was shorter for abbreviated fasting (10 versus 16 days, p=0.001), as well as the length of inhospital stay (2 versus 4 days, p=0.009). Hospital costs were lower in the abbreviated fasting (331 versus 682 reais, p<0.001). The univariable analysis revealed a correlation between complete oral intake and abbreviated fasting HR 0.29 (IC95%: 0.12-0.68 and abdominal distension HR 0.12 (IC95% 0.01-0.94). After multivariable analysis, abbreviated fasting presented a lower time for complete oral intake HR 0.39 (IC95%: 0.16-0.92. Conclusion: the abbreviated preoperative fasting favors the metabolic-nutritional recovery, reducing the time for complete oral intake. The implementation of the abbreviation protocol reduces hospital admission costs.
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