Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Dig Dis Sci ; 66(4): 1195-1211, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32415564

RESUMO

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.


Assuntos
Antineoplásicos/administração & dosagem , Esôfago de Barrett/tratamento farmacológico , Esôfago de Barrett/genética , Gluconatos/administração & dosagem , Análise de Sequência de RNA/métodos , Administração Oral , Adulto , Idoso , Esôfago de Barrett/diagnóstico , Quimioprevenção/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/prevenção & controle , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Projetos Piloto , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/prevenção & controle , Estudos Prospectivos
2.
Dig Dis Sci ; 51(12): 2326-36, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17103306

RESUMO

Using orally administered sucrose as a probe of gastrointestinal permeability, this study focused on determining whether Barrett's metaplasia exhibits a paracellular transepithelial leak to small nonelectrolytes. Subjects in five separate classes (nonendoscoped, asymptomatic controls; endoscoped, asymptomatic controls; gastroesophageal reflux disease without mucosal complications; grossly visible esophagitis; and Barrett's esophagus) consumed a sucrose solution at bedtime and collected all overnight urine. Urine volume was measured and sucrose concentration was determined by high-performance liquid chromatography. Patients with Barrett's were observed to exhibit a transepithelial leak to sucrose whose mean value was threefold greater than that seen in healthy control subjects or patients with reflux but without any mucosal defect. A parallel study of claudin tight junction proteins in endoscopy biopsy samples showed that whereas Barrett's metaplasia contains dramatically more claudin-2 and claudin-3 than is found in normal esophageal mucosa, it is markedly lower in claudins 1 and 5, indicating very different tight junction barriers.


Assuntos
Esôfago de Barrett/fisiopatologia , Permeabilidade da Membrana Celular/fisiologia , Células Epiteliais/metabolismo , Sacarose/farmacocinética , Amilases/sangue , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Biópsia , Estudos de Casos e Controles , Claudina-1 , Claudina-3 , Claudina-5 , Claudinas , Células Epiteliais/patologia , Esôfago/citologia , Esôfago/metabolismo , Esôfago/fisiologia , Humanos , Proteínas de Membrana/metabolismo , Metaplasia/metabolismo , Metaplasia/patologia , Metaplasia/fisiopatologia , Sacarose/urina , Junções Íntimas/metabolismo , Junções Íntimas/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...