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1.
Ned Tijdschr Geneeskd ; 162: D1712, 2018.
Artigo em Holandês | MEDLINE | ID: mdl-29350118

RESUMO

Optimal patient education prior to colonoscopy is essential for an optimal outcome of the procedure. Patients benefit from adequate information regarding laxatives, risks and alternatives, and must provide informed consent. The endoscopist also has to have access to patient data in advance of the procedure in order to carry out an adequate risk assessment for the use of sedation. Most centres in the Netherlands usually make use of a pre-endoscopy consultation to exchange this information, but here is now pressure on this practice because the number of colonoscopies is increasing rapidly as a result of the introduction of the national screening programme for colorectal cancer.


Assuntos
Colonoscopia , Neoplasias Colorretais/diagnóstico , Internet , Educação de Pacientes como Assunto/métodos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Consentimento Livre e Esclarecido , Países Baixos , Medição de Risco
2.
Sci Rep ; 6: 36199, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27808171

RESUMO

Acute myeloid leukemia (AML) can display de novo or acquired resistance to cytosine arabinoside (Ara-C), a primary component of induction chemotherapy. To identify genes capable of independently imposing Ara-C resistance, we applied a genome-wide CRISPR library to human U937 cells and exposed to them to Ara-C. Interestingly, all drug resistant clones contained guide RNAs for DCK. To avoid DCK gene modification, gRNA resistant DCK cDNA was created by the introduction of silent mutations. The CRISPR screening was repeated using the gRNA resistant DCK, and loss of SLC29A was identified as also being capable of conveying Ara-C drug resistance. To determine if loss of Dck results in increased sensitivity to other drugs, we conducted a screen of 446 FDA approved drugs using two Dck-defective BXH-2 derived murine AML cell lines and their Ara-C sensitive parental lines. Both cell lines showed an increase in sensitivity to prednisolone. Guide RNA resistant cDNA rescue was a legitimate strategy and multiple DCK or SLC29A deficient human cell clones were established with one clone becoming prednisolone sensitive. Dck-defective leukemic cells may become prednisolone sensitive indicating prednisolone may be an effective adjuvant therapy in some cases of DCK-negative AML.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Citarabina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Biblioteca Gênica , Testes Genéticos , Genoma Humano , Leucemia Mieloide Aguda/tratamento farmacológico , Animais , Sequência de Bases , Linhagem Celular , Células Clonais , Citarabina/farmacologia , DNA Complementar/genética , Desoxicitidina Quinase/genética , Dexametasona/farmacologia , Transportador Equilibrativo 1 de Nucleosídeo/genética , Loci Gênicos , Glucocorticoides/farmacologia , Humanos , Concentração Inibidora 50 , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/genética , Camundongos , Mutação/genética , Prednisolona/farmacologia , RNA Guia de Cinetoplastídeos/genética , Receptores de Glucocorticoides/metabolismo , Reprodutibilidade dos Testes , Células U937
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