RESUMO
Indomethacin (INDO) has a mechanism of action based on inhibiting fatty acids cyclooxygenase activity within the inflammation process. The action mechanism could be correlated with possible anticancer activity, but its high toxicity in normal tissues has made therapy difficult. By the coprecipitation method, the drug carried in a layered double hydroxides (LDH) hybrid matrix would reduce its undesired effects by promoting chemotherapeutic redirection. Therefore, different samples containing INDO intercalated in LDH were synthesized at temperatures of 50, 70, and 90 °C and synthesis times of 8, 16, 24, and 48 h, seeking the best structural organization. X-ray diffraction (XRD), vibrational Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), spectrophotometric analysis in UV-VIS, and differential thermogravimetric analysis (TGA/DTA) were used for characterization. Our results indicate that higher temperatures and longer synthesis time through coprecipitation reduce the possibility of INDO intercalation. However, it was possible to establish a time of 16 h and a temperature of 50 °C as the best conditions for intercalation. In vitro results confirmed the cell viability potential and anticancer activity in the LDH-INDO sample (16 h and 50 °C) for gastric cancer (AGP01, ACP02, and ACP03), breast cancer (MDA-MB-231 and MCF-7), melanoma (SK-MEL-19), lung fibroblast (MRC-5), and non-neoplastic gastric tissue (MN01) by MTT assay. Cell proliferation was inhibited, demonstrating higher and lower toxicity against MDA-MB-231 and SK-MEL-19. Thus, a clinical redirection of INDO is suggested as an integral and adjunctive anticancer medication in chemotherapy treatment.
Assuntos
Antineoplásicos , Hidróxidos , Indometacina , Nanopartículas , Humanos , Nanopartículas/química , Indometacina/farmacologia , Indometacina/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Hidróxidos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proliferação de Células/efeitos dos fármacosRESUMO
Microfluidic platforms for clinical use are a promising translational strategy for cancer research specially for drug screening. Identifying cancer stem cells (CSC) using sphere culture techniques in microfluidic devices (MDs) showed to be better reproducing physiological responses than other in vitro models and allow the optimization of samples and reagents. We evaluated individual sphere proliferation and stemness toward chemotherapeutic treatment (CT) with doxorubicin and cisplatin in bladder cancer cell lines (MB49-I and J82) cultured in MDs used as CSC treatment response platform. Our results confirm the usefulness of this device to evaluate the CT effect in sphere-forming efficiency, size, and growth rate from individual spheres within MDs and robust information comparable to conventional culture plates was obtained. The expression of pluripotency genetic markers (Oct4, Sox2, Nanog, and CD44) could be analyzed by qPCR and immunofluorescence in spheres growing directly in MDs. MDs are a suitable platform for sphere isolation from tumor samples and can provide information about CT response. Microfluidic-based CSC studies could provide information about treatment response of cancer patients from small samples and can be a promising tool for CSC-targeted specific treatment with potential in precision medicine. KEY MESSAGES: We have designed a microfluidic platform for CSC enriched culture by tumor sphere formation. Using MDs, we could quantify and determine sphere response after CT using murine and human cell lines as a proof of concept. MDs can be used as a tumor-derived sphere isolation platform to test the effect of antitumoral compounds in sphere proliferation.
Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/metabolismo , Neoplasias/metabolismoRESUMO
Se realizó un estudio observacional, descriptivo y longitudinal de 60 pacientes con cáncer primario del segmento hepatobiliopancreático, operados y egresados vivos del Servicio de Cirugía General del Hospital Provincial Docente Clinicoquirúrgico "Saturnino Lora Torres" de Santiago de Cuba, desde el 2005 hasta el 2011, con vistas a caracterizarles según variables seleccionadas. Entre las localizaciones más frecuentes figuraron: páncreas, hígado, vesícula y vías biliares extrahepáticas, en pacientes de la sexta década de la vida del sexo masculino; aunque el tumor de vesícula biliar prevaleció en las féminas. La estadificación clínica de la mayoría correspondió a las etapas más avanzadas, limitada al tratamiento quirúrgico paliativo. Los pacientes con factores de riesgo deben ser dispensarizados en las áreas de atención primaria de salud para que acudan al nivel secundario en etapas iniciales de la enfermedad, y puedan recibir el tratamiento quirúrgico con intención curativa, lo cual mejora su pronóstico y calidad de vida.
An observational, descriptive and longitudinal study of 60 patients with primary cancer of the hepato-bilio-pancreatic segment, operated and discharged alive from the General Surgery Service of "Saturnino Lora Torres" Teaching Provincial Hospital in Santiago de Cuba was carried out from 2005 to 2011, with the aim of characterizing them according to selected variables. Among the most frequent localizations there were: pancreas, liver, vesicle and biliary extrahepatic pathways, in patients of the sixth decade of the life, male sex; although the tumour of biliary vesicle prevailed in the females. The clinical staging of most corresponded to the most advanced stages, limited to the surgical palliative treatment. Patients with risk factors should be classified in the primary health care areas, so as to go to the secondary level in initial stages of the disease, and they can receive the surgical treatment with healing purposes, which improves their prognosis and life quality.