ABSTRACT
The most aggressive type of brain tumor is glioblastoma multiforme, which to date remains incurable. Thuja occidentalis is used in homeopathy for the treatment of cancer, however, its mechanism of action remains unknown. We set out to study the effects of thujone fractions of Thuja on glioblastoma using in vitro and in vivo models. We found that the α/ ß-thujone fraction decrease the cell viability and exhibit a potent anti-proliferative, pro-apoptotic and anti-angiogenic effects in vitro. In vivo assays showed that α /ß-thujone promotes the regression of neoplasia and inhibits the angiogenic markers VEGF, Ang-4 and CD31 into the tumor.
Subject(s)
Antineoplastic Agents/pharmacology , Glioblastoma/drug therapy , Monoterpenes/pharmacology , Phytotherapy , Plant Extracts/pharmacology , Thuja , Angiogenesis Inhibitors/pharmacology , Animals , Apoptosis/drug effects , Bicyclic Monoterpenes , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Glioblastoma/blood supply , Glioblastoma/pathology , Glioblastoma/physiopathology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/physiology , Humans , Male , Neoplasm Transplantation , Rats, Sprague-DawleyABSTRACT
RESUMEN Introducción: En los pacientes críticos con COVID-19 ocurren una serie de alteraciones metabólicas, las cuales afectan directamente el estado nutricional del paciente. Para mejorar la sobrevida de los pacientes con COVID-19, se hace relevante el tratamiento nutricional oportuno, idealmente dentro de las primeras 24-48 horas de la admisión a la UCI. El objetivo de este estudio fue reportar la evolución, desde el ingreso hasta el egreso, del balance nitrogenado, diversos parámetros bioquímicos y el estado nutricional de los pacientes con neumonía por COVID-19. Método: Estudio observacional retrospectivo de temporalidad longitudinal, se realizó en la UCI del Hospital Las Higueras de Talcahuano, Chile. Se incluyeron a 33 pacientes al ingreso y al egreso de la UCI. Resultados: Se reportó un incremento significativo del balance nitrogenado al egreso de los pacientes de UCI, sin embargo, no se registraron cambios en la media de talla, peso, IMC, prevalencia de desnutrición durante la estancia en la UCI. La prevalencia de desnutrición moderada y severa fue de un 14,0%, valor inferior al 45,0% informado en pacientes con COVID-19. Conclusión: En este estudio se reportó que la implementación del protocolo y la terapia nutricionales durante la pandemia de COVID-19 se asoció a un aumento del balance nitrogenado y un mejor control glicémico en los pacientes que egresan de la UCI por neumonía de COVID-19.
ABSTRACT Introduction: In critically ill patients with COVID-19, a series of metabolic alterations occur, which directly affect the patient's nutritional status. To improve the survival of patients with COVID-19, timely nutritional treatment is relevant, ideally within the first 24-48 hours of admission to the ICU. The objective of this study was to report the evolution, from admission to discharge, of the nitrogen balance, various biochemical parameters and the nutritional status of patients with COVID-19 pneumonia. Method: We conducted a retrospective observational study in the ICU of Las Higueras Hospital in Talcahuano, Chile. Thirty-three patients were included at admission and discharge from the ICU. Results: A significant increase in nitrogen balance was reported at ICU patient discharge, however, no changes were recorded in mean height, weight, BMI, or prevalence of malnutrition during ICU stay. The prevalence of moderate and severe malnutrition was 14.0%, a value lower than the 45.0% reported in patients with COVID-19. Discussion: In this study we reported that the implementation of the nutritional protocol and therapy during the COVID-19 pandemic was associated with an increase in nitrogen balance and better glycemic control in patients discharged from the ICU due to COVID-19 pneumonia.
ABSTRACT
MRP1 transporter correlates positively with glioma malignancy and the Multiple Drug Resistance (MDR) phenotype in Glioblastoma Multiforme (GBM). Evidence shows that the MRP1 transporter is controlled by the adenosine signalling axis. The aim of this study was to identify the role of adenosine on the MDR phenotype in Glioblastoma Stem-like Cells (GSCs), the cell population responsible for the tumorigenic and chemoresistance capabilities of this tumour. We found that GSCs have increased intrinsic capacity to generate extracellular adenosine, thus controlling MRP1 transporter expression and activity via activation of the adenosine A3 receptor (A3AR). We showed PI3K/Akt and MEK/ERK1/2 signaling pathways downstream A3AR to control MRP1 in GSCs. In vitro pharmacological blockade of A3AR had a chemosensitizing effect, enhancing the actions of antitumour drugs and decreasing cell viability and proliferation of GSCs. In addition, we produced an in vivo xenograft model by subcutaneous inoculation of human GSCs in NOD/SCID-IL2Rg null mice. Pharmacological blockade of A3AR generated a chemosensitizing effect, enhancing the effectiveness of the MRP1 transporter substrate, vincristine, reducing tumour size and the levels of CD44 and Nestin stem cell markers as well as the Ki-67 proliferation indicator. In conclusion, we demonstrated the chemosensitizing effect of A3AR blockade on GSCs.