RESUMEN
Grape seed procyanidin extract (GSE) had been reported to exert antineoplastic properties in preclinical studies. A modified phase I, open-label, dose-escalation clinical study was conducted to evaluate the safety, tolerability, MTD, and potential chemopreventive effects of leucoselect phytosome (LP), a standardized GSE complexed with soy phospholipids to enhance bioavailability, in heavy active and former smokers. Eight subjects ages 46-68 years were enrolled into the study and treated with escalating oral doses of LP for 3 months. Bronchoscopies with bronchoalveolar lavage and bronchial biopsies were performed before and after 3 months of LP treatment. Hematoxylin and eosin stain for histopathology grading and IHC examination for Ki-67 proliferative labeling index (Ki-67 LI) were carried out on serially matched bronchial biopsy samples from each subject to determine responses to treatment. Two subjects were withdrawn due to issues unrelated to the study medication, and a total of 6 subjects completed the full study course. In general, 3 months of LP, reaching the highest dose per study protocol was well tolerated and no dosing adjustment was necessary. Such a treatment regimen significantly decreased bronchial Ki-67 LI by an average of 55% (P = 0.041), with concomitant decreases in serum miR-19a, -19b, and -106b, which were oncomirs previously reported to be downregulated by GSE, including LP, in preclinical studies. In spite of not reaching the original enrollment goal of 20, our findings nonetheless support the continued clinical translation of GSE as an antineoplastic and chemopreventive agent against lung cancer.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Biflavonoides/administración & dosificación , Catequina/administración & dosificación , Extracto de Semillas de Uva/administración & dosificación , Neoplasias Pulmonares/prevención & control , Proantocianidinas/administración & dosificación , Administración Oral , Anciano , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/química , Apoptosis , Biflavonoides/efectos adversos , Biflavonoides/química , Biopsia , Bronquios/diagnóstico por imagen , Bronquios/efectos de los fármacos , Bronquios/patología , Broncoscopía , Catequina/efectos adversos , Catequina/química , Proliferación Celular , Regulación hacia Abajo/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Extracto de Semillas de Uva/efectos adversos , Extracto de Semillas de Uva/química , Humanos , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/genética , Masculino , MicroARNs/sangre , MicroARNs/metabolismo , Persona de Mediana Edad , Proantocianidinas/efectos adversos , Proantocianidinas/química , Fumar/efectos adversos , Resultado del TratamientoRESUMEN
Endobronchial ultrasound-guided transbronchial needle aspiration has a low complication rate and is a cost-effective procedure for mediastinal staging and diagnosis when compared with the more invasive mediastinoscopy. There are increasing case reports of unexpected complications including equipment failures with and without significant medical consequences. Knowledge of complications, including those that are rare, is essential for the physician performing this minimally invasive procedure. We report a case of a retained foreign body from the unexpected separation of a distal spring/coil mechanism from the Olympus ViziShot Aspiration needle following early needle deployment within the working channel of the bronchoscope.