RESUMO
BACKGROUND: Intestinal metaplasia (IM) is a gastric cancer precursor lesion (GCPL) and an extremely high risk factor for progression to gastric cancer (GC). Clinical guidelines recommend that patients with extensive IM undergo a gastroscopy every 3 years. However, protein biomarkers that indicate a transition from IM to GC are lacking. Our group recently identified an interferon-alpha (IFNα)-responsive gene, Schlafen 4 (Slfn4), in immune cells that correlates with metaplastic changes in Helicobacter-infected mice. We therefore tested the hypothesis that a human homolog of Slfn4, namely, Schlafen 5 (SLFN5), correlates with progression of GCPL to GC. METHODS: Jurkat T-lymphoid and HL-60 myeloid cell lines were treated with IFNα, and SLFN5 mRNA was quantified by quantitative PCR. SLFN5 protein expression in the inflamed gastric mucosa was co-localized to specific immune cell types by immunohistochemistry using CD20, CD2, and MAC2 antibodies. SLFN5 expression was also determined by immunohistochemistry in formalin-fixed paraffin-embedded samples from individuals with non-atrophic gastritis, atrophic gastritis, complete IM, incomplete IM, and GC, respectively. RESULTS: The IFNα treatment of Jurkat and HL-60 cells induced SLFN5 mRNA. SLFN5 protein was expressed mainly by T lymphocytes in inflamed gastric mucosa. The highest level of SLFN5 expression was observed in patients with IM that progressed to GC. Receiver operating characteristic curves demonstrated that correlating SLFN5 expression with the histologic diagnosis of IM significantly increased the probability of identifying patients who may progress to GC. CONCLUSION: In this study population, elevated SLFN5 protein expression in patients with IM correlated with progression to GC.
Assuntos
Proteínas de Ciclo Celular/genética , Interferon-alfa/administração & dosagem , Intestinos/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Células HL-60 , Humanos , Imuno-Histoquímica , Células Jurkat , Masculino , Metaplasia , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Linfócitos T/metabolismo , Adulto JovemRESUMO
BACKGROUND: The angiotensin converting enzyme (ACE) is a key protein of the renin angiotensin system, whose main function is the conversion of angiotensin I to II. ACE is involved in the physiological control of blood pressure and it is a candidate gene for essential hypertension in humans. We tested the relevance of the ACE insertion/deletion (I/D) polymorphism in our population. METHODS: We recruited 243 hypertensive and 407 normotensive subjects in the city of Havana, matched according to age, sex and ethnic group. The ACE (I/D) polymorphism was determined by the polymerase chain reaction (PCR) technique. The fit of genotype frequencies to Hardy-Weinberg proportions was evaluated in all groups analyzed. The possible association between the ACE I/D polymorphism and hypertension status was tested by chi2 and odds ratio tests. RESULTS: All groups but black female cases were in Hardy-Weinberg equilibrium. The frequencies of the D allele in hypertensive/normotensive subjects were 0.61/0.59 in white males, 0.58/0.58 in white females, 0.47/0.59 in black males and 0.58/0.54 in black females. The distribution of ACE genotypes differed significantly between cases and controls only in black women according to the additive model (chi2p=0.04) but the adjusted OR did not show significant association (OR 1.14 95% CI 0.62 to 2.10). CONCLUSION: The ACE I/D polymorphism was not associated with hypertension in our multiethnic sample. While the chi2 test for additive model in black women suggested a marginal significance, the adjusted OR did not show any significant association.
Assuntos
Hipertensão/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , População Negra , Cuba , Feminino , Genótipo , Humanos , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , População BrancaRESUMO
El Código Genético Standard (CGS) no es el resultado de un proceso de asignación aleatoria de aminoácidos a codones, sino más bien todo lo contrario, determinadas regularidades estructurales que lo distinguen y que tienen profundas consecuencias en las propiedades de las secuencias biológicas actuales y en sus patrones evolutivos, revelan el resultado de la acción de ciertas leyes. La bioinformática ha jugado un rol central no sólo en la evaluación de la repercusión de estas características del CGS sino también en la búsqueda de las causas, las fuerzas químico-fisicas, los mecanismos evolutivos que conformaron su estructura actual o los que dieron lugar a algunas de sus variantes nucleares u organulares.En general el desarrollo de las informática han revolucionado la metodología de las ciencias empíricas, un nuevo empirismo in silico han permitido la implementación de modelos matemáticos y la ejecución de nuevos experimentos de validación con ventajas enormes en cuanto a costo y tiempo, la biología evolutiva no ha sido ajena a la influencia de estos cambios, en este trabajo se podrá apreciar la decisiva participación de diferentes métodos computacionales en la aclaración aún incompleta de algunas incógnitas relacionadas con el CGS(AU)
