ABSTRACT
INTRODUCCIÓN: La leucemia mieloide aguda (LMA) constituye un grupo de trastornos heterogéneos de las células madre hematopoyéticas caracterizados por una maduración incompleta de las células sanguíneas y uma producción reducida de otras células hematopoyéticas normales. Se presenta con mayor frecuencia en personas mayores, aunque puede presentarse también en jóvenes y niños. DESCRIPCIÓN DE LA TECNOLOGÍA: El venetoclax es un inhibidor selectivo de la proteína antiapoptótica BCL-2 (proteína 2 de la Leucemia/Linfoma de Células B) que se administra por vía oral. OBJETIVO: El objetivo del presente informe es evaluar la eficacia, seguridad e impacto presupuestario del venetoclax combinado con azacitidina, decitabina o dosis bajas de citarabina para el tratamiento de la leucemia mieloide aguda en pacientes de mayores a 75 años o con comorbilidades que no les permita recibir quimioterapia intensiva de inducción. METODOLOGÍA: Se priorizó la inclusión de revisiones sistemáticas (RS) y metaanálisis (MA), ensayos clínicos controlados aleatorizados (ECCA), guías de práctica clínica basadas en evidencia, evaluaciones de tecnologías sanitarias y estudios observacionales de adecuado diseño para los aspectos de eficacia, efectividad clínica, seguridad y/o efectos adversos. Se consideró además cualquier publicación directa o indirecta que mencionara el tema em cuestión. Se recabaron datos de eficacia en desenlaces clínicamente relevantes (sobrevida global, respuesta completa, mejora en la calidad de vida) y de efectos adversos relacionados con el uso de venetoclax. RESULTADOS: Realizando la búsqueda en las bases de datos de información biomédica utilizadas hasta el día 2 de noviembre de 2020 fueron identificados y seleccionados dos ensayos clínicos controlados (ECA), que cumplen los criterios de inclusión según la pregunta PICO establecida. CONCLUSIONES: Con evidencia de alta calidad a un año de seguimiento se observó que el uso de venetoclax asociado a hipometilantes presenta beneficios moderados en la evolución clínica de los pacientes frágiles con LMA en comparación con el uso solamente de hipometilantes o citarabina en dosis bajas, con un aumento moderado de riesgo de eventos adversos. Probablemente, la adopción de la tecnología signifique un gasto extenso de recursos con los precios corrientes del venetoclax, y por este motivo el impacto económico favorecería a las terapias disponibles con análogos de las pirimidinas. Completando el proceso de evaluación de la evidencia científica y económica, la votación sobre los atributos del marco de valor realizado por la Mesa Técnica y el análisis final de la Mesa de Recomendaciones, la CONETEC sugiere no cubrir el venetoclax en esta indicación.
Subject(s)
Humans , Leukemia, Myeloid, Acute/drug therapy , Apoptosis Regulatory Proteins/antagonists & inhibitors , Technology Assessment, Biomedical , Cost-Benefit AnalysisABSTRACT
PURPOSE: The purpose of this study is to determine the association between the BIK/NBK gene expression and estrogen receptor alpha expression. MATERIALS AND METHODS: We determined the association of BIK/NBK gene expression by real time quantitative reverse transcription polymerase chain reaction and estrogen receptor alpha expression by immunohistochemistry in samples of breast cancer tissue. RESULTS: We found a statistically significant correlation of BIK/NBK gene expression with the estrogen receptor alpha expression (ρ = 0.751, p = 0.004). For verify differences of BIK/NBK gene expression among ERα+ and ERα- breast cancer tissues, Mann-Whitney U test was performed, obtaining significant differences. CONCLUSIONS: BIK/NBK gene expression may have important clinical implications and provide predictive, prognostic or therapeutic marker in breast cancer patients according to the estrogen receptor alpha expression (AU)
Subject(s)
Humans , Female , Apoptosis Regulatory Proteins/genetics , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Membrane Proteins/genetics , Biomarkers, Tumor/genetics , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/metabolism , Biomarkers, Tumor/antagonists & inhibitors , Biomarkers, Tumor/metabolismABSTRACT
Auto-transplantation of adipose tissue is commonly used for the treatment of tissue defects in plastic surgery. The survival of the transplanted adipose tissue is not always constant, and one of reasons is the accelerated apoptosis of the implanted preadipocytes. We have recently established highly homogeneous preadipocytes, named ccdPAs. The aim of the current study was to evaluate the regulation of the potency of platelet-rich plasma (PRP) on the apoptosis of ccdPAs in vitro. PRP stimulated the proliferation of the preadipocytes in a dose-dependent manner, and the stimulatory activity of 2% PRP was significantly higher than that of 2% FBS or 2% platelet-poor plasma (PPP). The presence of 2% PRP significantly inhibited serum starvation- or TNF-alpha/cycloheximide-induced apoptosis in comparison to 2% FBS or 2% PPP. DAPK1 and Bcl-2-interacting mediator of cell death (BIM) mRNAs were reduced in the preadipocytes cultured with 2% PRP in comparison to those cultured in 2% FBS. The gene expression levels were significantly higher in cells cultured without serum in comparison to cells cultured with 2% FBS, and the levels in the cells with 2% PRP were reduced to 5-10% of those in the cells without serum. These results indicated that ccdPAs exhibit anti-apoptotic activities, in addition to increased proliferation, when cultured in 2% PRP in comparison to the same concentration of FBS, and that this was accompanied with reduced levels of DAPK1 and BIM mRNA expression in in vitro culture. PRP may improve the outcome of transplantation of adipose tissue by enhancing the anti-apoptotic activities of the implanted preadipocytes.
Subject(s)
Humans , Adipocytes/cytology , Adipose Tissue/cytology , Apoptosis/physiology , Apoptosis Regulatory Proteins/antagonists & inhibitors , Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors , Cell Culture Techniques/methods , Cell Differentiation , Cell Proliferation , Cells, Cultured , Gene Expression Regulation , Membrane Proteins/antagonists & inhibitors , Platelet-Rich Plasma/metabolism , Proto-Oncogene Proteins/antagonists & inhibitors , Tissue TransplantationABSTRACT
Apoptosis serves to remove excess or damaged cells and its dysregulation may lead to a number of pathological disorders including cancer. Studies during the last 20 years have unravelled much of the molecular mechanisms that control apoptosis. Whether a cell dies in response to diverse apoptotic stimuli, including DNA-damaging agents, is determined largely by interactions between proteins of the Bcl-2 family. A death signal is transmitted through the BH3-only proteins to Bax and Bak which in turn permeabilise the outer mitochondrial membrane allowing the release of apoptogenic factors, which triggers activation of cell-deathpromoting caspases. These proteolytic enzymes are tightly controlled by members of the inhibitor of apoptosis (IAP) family. Activation of the caspase cascade via cell death receptors also represents a key apoptotic pathway in both normal and tumour cells. Basic knowledge of these apoptosis regulators provides the basis for novel therapeutic strategies aimed at promoting tumour cell death or enhancing susceptibility to apoptotic inducers. This review focuses on these strategies (AU)