RESUMEN
The mistletoe lectin viscumin (MLI) is a ribosome-inactivating protein from Viscum album widely used in cancer therapy. Its antitumor properties are due to its immunomodulating action, previously demonstrated in experiments involving intravenous, subcutaneous, and oral administration of viscumin. To investigate whether viscumin has a cytotoxic effect on the intestinal epithelium, its safety was assessed using (i) impedance spectroscopy to measure the integrity of the colorectal adenocarcinoma Caco-2 cell monolayer after exposure to viscumin and (ii) a novel technique of determining the portion of viscumin-inactivated ribosomes. It was shown that inactivation of at least 20% of the ribosomes within 6 h did not lead to disruption of the Caco-2 cell monolayer or alter the physicochemical parameters of enterocyte membranes.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Proteínas Inactivadoras de Ribosomas Tipo 2/farmacología , Ribosomas/efectos de los fármacos , Toxinas Biológicas/farmacología , Células CACO-2 , Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Impedancia Eléctrica , Enterocitos/efectos de los fármacos , Humanos , Ribosomas/genéticaRESUMEN
Viscumin (mistletoe lectin I, MLI) in concentrations of 10-11-10-7 M causes endoplasmic reticulum stress and triggers unfolded protein response, a modulator of antitumor immunity, in target cells.
Asunto(s)
Estrés del Retículo Endoplásmico , Proteínas Inactivadoras de Ribosomas Tipo 2/farmacocinética , Toxinas Biológicas/farmacocinética , Animales , Células CACO-2 , Línea Celular Tumoral , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Inyecciones Subcutáneas , Masculino , Ratones , Lectinas de Plantas/administración & dosificación , Lectinas de Plantas/farmacocinética , Lectinas de Plantas/farmacología , Proteínas Inactivadoras de Ribosomas Tipo 2/administración & dosificación , Proteínas Inactivadoras de Ribosomas Tipo 2/farmacología , Toxinas Biológicas/administración & dosificación , Toxinas Biológicas/farmacología , Respuesta de Proteína Desplegada/efectos de los fármacosRESUMEN
The efficiency of autoregulation of the coronary blood flow and contractile activity of the myocardium in the presence of inhibitors of constitutive and inducible NO synthases was studied in rats exposed to 6-h restraint stress. Intracoronary administration of S-methylisothiourea (10 µmol/liter), but not L-NAME (60 µmol/liter) fully prevented post-stress increase in the volume coronary blood flow rate, intensity of heart perfusion, and reduction of ventricular developed pressure at all levels of perfusion pressure. Real-time PCR showed 6-fold increased expression of inducible NO-synthase mRNA in the heart tissue against the background of unchanged expression of neuronal and endothelial NO synthases and 2-3-fold elevated content of transcripts of stress-inducible genes Hspa1a and Hspbp1. It was shown that the hypotension of coronary vessels and reduced contractile function of the myocardium are related to NO production by inducible NO synthase in endotheliocytes of coronary vessels and cardiomyocytes.
Asunto(s)
Circulación Coronaria/fisiología , Homeostasis/fisiología , Contracción Miocárdica/fisiología , Óxido Nítrico Sintasa/metabolismo , Restricción Física/efectos adversos , Estrés Fisiológico/fisiología , Animales , Circulación Coronaria/efectos de los fármacos , Cartilla de ADN/genética , Isotiuronio/análogos & derivados , Isotiuronio/farmacología , Masculino , Contracción Miocárdica/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Espectrofotometría , Estadísticas no Paramétricas , Presión Ventricular/efectos de los fármacos , Presión Ventricular/fisiologíaRESUMEN
Inflammatory breast cancer is characterized by high malignancy, early and rapid lymphogenic and hematogenic metastasizing, and high mortality. The diagnosis of this form of cancer is based fully on the clinical criteria. Whole transcriptome analysis of tumor tissue specimens from patients with inflammatory breast cancer detected 137 differentially expressed mRNA (17 genes with low expression and 120 with high expression). Genes involved in the organization of inflammatory process, chemotaxis, and transcription regulation were active in the process of pathogenesis of inflammatory breast cancer.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias Inflamatorias de la Mama/genética , Proteínas de Neoplasias/genética , ARN Mensajero/genética , Transcriptoma , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Quimiotaxis/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Neoplasias Inflamatorias de la Mama/patología , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
Hyperexpression of HER-2/neu is found in tissues of 25-30% patients with primary breast cancer. Monotherapy with antitumor drug trastuzumab as second-third line therapy and its combination with cytostatics prolong the interval before disease progress and the overall survival of patients with metastatic HER-2/neu+ tumors. Trastuzumab is now prescribed after evaluation of HER-2/neu status by the immunohistochemical method and/or fluorescent in situ hybridization. We have developed a method for evaluating the HER-2/neu status of breast cancer biopsy specimens by real time reverse transcription PCR. Based on the analysis of published data, six candidate genes in the pericentromer region of chromosome 17 are selected for data normalization. Stability of these genes is verified on the cell model (MCF-7 and SK-BR-3) and on biopsy materials. The sensitivity and specificity of the method is evaluated on a collection of biopsy specimens.