RESUMO
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 Two subjects were withdrawn due to issues unrelated to the study medication, and a total of 6 subjects completed the full study course.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.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Biflavonoides/administração & dosagem , Catequina/administração & dosagem , Extrato de Sementes de Uva/administração & dosagem , Neoplasias Pulmonares/prevenção & controle , Proantocianidinas/administração & dosagem , Administração Oral , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/química , Apoptose , Biflavonoides/efeitos adversos , Biflavonoides/química , Biópsia , Brônquios/diagnóstico por imagem , Brônquios/efeitos dos fármacos , Brônquios/patologia , Broncoscopia , Catequina/efeitos adversos , Catequina/química , Proliferação de Células , Regulação para Baixo/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Extrato de Sementes de Uva/efeitos adversos , Extrato de Sementes de Uva/química , Humanos , Antígeno Ki-67/análise , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Masculino , MicroRNAs/sangue , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proantocianidinas/efeitos adversos , Proantocianidinas/química , Fumar/efeitos adversos , Resultado do TratamentoAssuntos
Brônquios/cirurgia , Broncopatias/cirurgia , Dilatação/métodos , Stents , Brônquios/diagnóstico por imagem , Broncopatias/diagnóstico , Broncopatias/etiologia , Broncoscopia , Constrição Patológica/diagnóstico , Constrição Patológica/cirurgia , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Tomografia Computadorizada por Raios XRESUMO
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.