RESUMEN
Synucleins are a family of small, soluble proteins mainly expressed in neural tissue and in certain tumors. Since their discovery, tens of thousands of scientific reports have been published about this family of proteins as they are associated with severe human diseases. Although the physiological function of these proteins is still elusive, their relationship with neurodegeneration and cancer has been clearly described over the years. In this review, we summarize data connecting synucleins and cancer, going from the structural description of these molecules to their involvement in tumor-related processes, and discuss the putative use of these proteins as cancer molecular biomarkers.
Asunto(s)
Neoplasias , alfa-Sinucleína , Humanos , alfa-Sinucleína/genética , Neoplasias/genéticaRESUMEN
BACKGROUND: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. AIM: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. MATERIAL AND METHODS: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. RESULTS: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. CONCLUSIONS: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.
Asunto(s)
Antieméticos/efectos adversos , Arritmias Cardíacas/inducido químicamente , Muerte Súbita Cardíaca/etiología , Domperidona/efectos adversos , Adulto , Femenino , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Náusea/tratamiento farmacológico , Oportunidad Relativa , Factores de Riesgo , Vómitos/tratamiento farmacológicoRESUMEN
Background: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. Aim: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. Material and Methods: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. Results: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. Conclusions: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.
Asunto(s)
Animales , Femenino , Humanos , Ratones , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Diterpenos/administración & dosificación , Compuestos Epoxi/administración & dosificación , Paclitaxel/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Diterpenos/química , Sinergismo Farmacológico , Compuestos Epoxi/química , Lactonas/administración & dosificación , Lactonas/química , Ratones Desnudos , Estrés Oxidativo/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Activación Transcripcional/efectos de los fármacos , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A short and efficient methodology for the synthesis of chiral dioxa-caged compounds from levoglucosenone, a biomass-derived enone, is herein presented. The key transformation, that involves a cascade 3-step cationic cyclization, was efficiently carried out in high yields and selectivities by Montmorillonite K-10 catalysis. The usefulness of K-10 in related semi-pinacol rearrangements to obtain pyran-3-ones is also shown. Interesting differences in the reactivity pattern was found for epimeric alcohols, and the origins of these findings were determined by DFT calculations.