RESUMO
Traditional Informed Consent is becoming increasingly inadequate, especially in the context of research biobanks. How much information is needed by patients for their consent to be truly informed? How does the quality of the information they receive match up to the quality of the information they ought to receive? How can information be conveyed fairly about future, non-predictable lines of research? To circumvent these difficulties, some scholars have proposed that current consent guidelines should be reassessed, with trust being used as a guiding principle instead of information. Here, we analyse one of these proposals, based on a Participation Pact, which is already being offered to patients at the Istituto Europeo di Oncologia, a comprehensive cancer hospital in Milan, Italy.
Assuntos
Bancos de Espécimes Biológicos , Pesquisa Biomédica/ética , Comportamento de Escolha , Consentimento Livre e Esclarecido , Autonomia Pessoal , Relações Pesquisador-Sujeito/ética , Confiança , Bancos de Espécimes Biológicos/ética , Bancos de Espécimes Biológicos/organização & administração , Compreensão , Contratos/ética , Contratos/tendências , Humanos , Disseminação de Informação , Consentimento Livre e Esclarecido/ética , Itália , Participação do Paciente , Relações Pesquisador-Sujeito/psicologia , Valores SociaisRESUMO
PURPOSE: Spiral computed tomography (CT) can detect lung cancer at an early stage, but the malignant potential is unknown. The question is, as follows: do these small lesions have the same lethal potential as do symptomatic tumors? EXPERIMENTAL DESIGN: We used a cDNA microarray platform and compared the gene expression profile of spiral CT-detected lung carcinomas with a matched case-control population of patients presenting with symptomatic lung cancer. RESULTS: CT-detected and symptomatic tumors have shown a comparable gene expression profile. Correspondence analysis has demonstrated that nine genes were differentially expressed, although with a high variability across the samples that prevented distinguishing the two groups of tumors. Analysis of these nine genes has suggested that early-detected tumors have higher levels of retinoic acid production and higher expression levels of caveolin 2, matrix Gla, and cystatin A, which are already known to be lost during tumor progression. CONCLUSIONS: All of the tumors observed are histologically malignant according to the WHO Classification. Early lung cancers that are detected by screening have a gene expression pattern similar to, but not identical to, that of symptomatic lung carcinomas.
Assuntos
DNA Complementar/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Tomografia Computadorizada Espiral/métodos , Idoso , Proteínas de Ligação ao Cálcio/biossíntese , Caveolina 2 , Caveolinas/biossíntese , Cistatinas/biossíntese , Progressão da Doença , Proteínas da Matriz Extracelular/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatística como Assunto , Tomografia Computadorizada por Raios X , Proteína de Matriz GlaRESUMO
Protein ubiquitination has been implicated in the regulation of axonal growth and synaptic plasticity as well as in the pathogenesis of neurodegenerative diseases. Here we show that depolarization-dependent Ca2+ influx into synaptosomes produces a global, rapid (range of seconds), and reversible decrease of the ubiquitinated state of proteins, which correlates with the Ca2+-dependent dephosphorylation of several synaptic proteins. A similar general decrease in protein ubiquitination was observed in nonneuronal cells on Ca2+ entry induced by ionomycin. Both in synaptosomes and in nonneuronal cells, this decrease was blocked by FK506 (a calcineurin antagonist). Proteins whose ubiquitinated state was decreased include epsin 1, a substrate for the deubiquitinating enzyme fat facets/FAM, which we show here to be concentrated at synapses. These results reveal a fast regulated turnover of protein ubiquitination. In nerve terminals, protein ubiquitination may play a role both in the regulation of synaptic function, including vesicle traffic, and in the coordination of protein turnover with synaptic use.