The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells.

Significant advances in understanding the molecular complexity of the development and progression of pancreatic cancer have been made, but this disease is still considered one of the most lethal human cancers and needs new therapeutic options. In the present study, the antineoplastic effects of AD80, a multikinase inhibitor, were investigated in models of pancreatic cancer. AD80 reduced cell viability and clonogenicity and induced polyploidy in pancreatic cancer cells. At the molecular level, AD80 reduced RPS6 and histone H3 phosphorylation and induced γH2AX and PARP1 cleavage. Additionally, the drug markedly decreased AURKA phosphorylation and expression. In PANC-1 cells, AD80 strongly induced autophagic flux (consumption of LC3B and SQSTM1/p62). AD80 modulated 32 out of 84 autophagy-related genes and was associated with vacuole organization, macroautophagy, response to starvation, cellular response to nitrogen levels, and cellular response to extracellular stimulus. In 3D pancreatic cancer models, AD80 also effectively reduced growth independent of anchorage and cell viability. In summary, AD80 induces mitotic aberrations, DNA damage, autophagy, and apoptosis in pancreatic cancer cells. Our exploratory study establishes novel targets underlying the antineoplastic activity of the drug and provides insights into the development of therapeutic strategies for this disease.

Perceptions of patients, physicians, and Medical students on physicians' appearance.

OBJECTIVE: To investigate the impressions made by different styles of dress and appearance adopted by physicians on patients, medical students and other physicians in Brazil. METHODS: Two hundred fifty nine patients, 119 students, and 99 physicians answered questions related to a panel of male and female physicians' pictures covering the following styles: white clothing; white coat; formal, informal, and casual garments; and surgical scrubs. They also reported their level of discomfort with a list of 20 items for professional appearance of both genders. RESULTS: Most of the answers of the volunteers involved using white clothes or white coat, and in many situations the percentages of preference referred for these styles were close. Physicians and students preferred physicians wearing surgical scrubs for emergency visits, and doctors with informal style for discussing psychological problems with male professionals. Patients most often chose white clothing in response to questions. Regarding male professionals, all three groups reported high degree of discomfort for the use of shorts and bermuda shorts, multiple rings, facial piercing, sandals, extravagant hair color, long hair, and earrings. For females, high levels of discomfort were reported to shorts, blouses exposing the belly, facial piercing, multiple rings, extravagant hair color, and heavy makeup. CONCLUSION: Brazilian patients, physicians, and medical students form a better initial impression of physicians using clothing traditionally associated with the profession and exhibiting more conventional appearance. The use of entirely white garments appears to be a satisfactory option in this country.

Impressões de pacientes, médicos e estudantes de medicina quanto a aparência dos médicos / Perceptions of patients, physicians, and medical students on physicians' appearance

OBJETIVO: Investigar as impressões causadas em pacientes, estudantes de Medicina e médicos brasileiros por diferentes estilos de vestimenta e aparência adotados pelos médicos. MÉTODOS: Participaram da pesquisa 259 pacientes, 119 estudantes e 99 médicos, respondendo questões relativas a um painel de fotos de médico e médica vestidos nos seguintes estilos: roupa branca, avental branco, avental social, formal, informal, casual e centro cirúrgico. Eles ainda registraram seu grau de desconforto frente uma lista de 20 itens de aparência para profissionais de ambos os sexos. RESULTADO: A maioria das respostas dos voluntários envolveu o uso de roupa branca ou avental branco, e em muitas questões os percentuais de preferência referidos para esses estilos foram muito próximos. Médicos e estudantes preferiram profissionais em traje de centro cirúrgico para consultas de urgência, e o estilo informal para discutir problemas psicológicos com profissional masculino. Os pacientes escolheram mais frequentemente a roupa branca em resposta às questões. No tocante aos profissionais masculinos, os três grupos referiram elevado grau de incômodo para o uso de shorts e bermudas, muitos anéis, piercing facial, sandálias, cabelos de cor extravagante, cabelos compridos e brincos. Para o sexo feminino, níveis elevados de desconforto foram assinalados para shorts, blusas mostrando a barriga, piercing facial, bermudas,muitos anéis, cabelos de cor extravagante e maquiagem carregada. CONCLUSÃO: Pacientes, médicos e estudantes de Medicina brasileiros desenvolvem melhor impressão inicial de médicos que utilizam trajes tradicionalmente associados com a profissão e de aparência mais convencional. O uso da vestimenta inteiramente branca parece ser opção satisfatória no Brasil.

OBJECTIVE: To investigate the impressions made by different styles of dress and appearance adopted by physicians on patients, medical students and other physicians in Brazil. METHODS: Two hundred fifty nine patients, 119 students, and 99 physicians answered questions related to a panel of male and female physicians' pictures covering the following styles: white clothing; white coat; formal, informal, and casual garments; and surgical scrubs. They also reported their level of discomfort with a list of 20 items for professional appearance of both genders. RESULTS: Most of the answers of the volunteers involved using white clothes or white coat, and in many situations the percentages of preference referred for these styles were close. Physicians and students preferred physicians wearing surgical scrubs for emergency visits, and doctors with informal style for discussing psychological problems with male professionals. Patients most often chose white clothing in response to questions. Regarding male professionals, all three groups reported high degree of discomfort for the use of shorts and bermuda shorts, multiple rings, facial piercing, sandals, extravagant hair color, long hair, and earrings. For females, high levels of discomfort were reported to shorts, blouses exposing the belly, facial piercing, multiple rings, extravagant hair color, and heavy makeup. CONCLUSION: Brazilian patients, physicians, and medical students form a better initial impression of physicians using clothing traditionally associated with the profession and exhibiting more conventional appearance. The use of entirely white garments appears to be a satisfactory option in this country.