RESUMEN
The aim of our trial was to evaluate the prognostic significance of qualitative ctDNA analysis on different stages of EGFR mutated non-small cell lung cancer (NSCLC) treatment. We included 99 patients amendable for the first line treatment with either gefitinib/erlotinib (n = 87), afatinib (n = 10) or osimertinib (n = 2). Sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 were performed before first dose, after 2 and 4 months of treatment, and on progression. Our analysis showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line tyrosine kinase inhibitors (TKIs) in terms of progression-free and overall survival. When treated with conventional approach, i.e. monotherapy with TKIs, the patients falls into three subgroups based on ctDNA analysis before and after 2 months of treatment. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 - 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 - 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcome of patients.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , ADN Tumoral Circulante , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , ADN Tumoral Circulante/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del TratamientoRESUMEN
We studied the effects of apoptotic bodies of cardiomyocytes (ApBc) and fibroblasts (ApBf) on myocardial regeneration and contractility in rats and the dynamics of RNA concentrations in cardiomyocytes and fibroblasts at different stages of apoptosis. ApBc increase the contractility of rat myocardium, while ApBf reduce it. ApBc stimulate the development of clones of cardiomyocyte precursors in the myocardium, while ApBf stimulate the formation of endothelial precursor clones. In doxorubicin cardiomyopathy, ApBc, similar to the reference drug (ACE inhibitor) improve animal survival, while ApBf produce no such effect. RNA concentrations in cardiomyocytes and fibroblasts before apoptosis and at the beginning of cell death significantly differed, while in apoptotic bodies of these cells, it was practically the same. It has been hypothesized that RNA complex present in ApBc and ApBf represents an "epigenetic code" of directed differentiation of cardiac stem cells.
Asunto(s)
Envejecimiento/metabolismo , Cardiomiopatías/metabolismo , Medios de Cultivo/farmacología , Vesículas Extracelulares/metabolismo , Fibroblastos/metabolismo , Miocitos Cardíacos/metabolismo , Células Madre/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Apoptosis/efectos de los fármacos , Cardiomiopatías/inducido químicamente , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/patología , Diferenciación Celular , Células Clonales , Medios de Cultivo/química , Doxorrubicina/toxicidad , Vesículas Extracelulares/química , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fosinopril/farmacología , Masculino , Contracción Miocárdica/efectos de los fármacos , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Cultivo Primario de Células , ARN/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Células Madre/citología , Células Madre/efectos de los fármacosRESUMEN
The purpose of this study was to establish the role of scintimammography with 99mTs-technetril for predicting pathological status of regional lymph nodes after neoadjuvant chemotherapy. In 123 primary patients with locally advanced breast cancer stage cT1-4N0-3M0 there was performed scintimammography: before treatment and after 2-3 cycles of neoadjuvant chemotherapy 63 patients; after 2-3 cycles of neoadjuvant chemotherapy and before surgery--in 5 patients; after 4-6 cycles of neoadjuvant chemotherapy--55 women. All patients were divided into 2 groups: the first included 68 patients whom scintimammography was performed before and after 2-3 cycles of neoadjuvant chemotherapy; the second--60 women whom scintimammography was performed before treatment and before surgery. In patients of the first group positive results were obtained in 16 (23.5%), negative--26 (38.3%), false positive--16 (23.5%) and false negative--10 (14.7%) cases. Sensitivity, specificity, overall accuracy, positive predictive value and negative results were 61.5%, 61.9%, 61.7%, 50% and 72.2%, respectively. During the scintimammography after 4-6 cycles of neoadjuvant chemotherapy positive results were observed in 17 (28.3%) negative--18 (30%), false positive--19 (31.7%) and false negative--6 (10%) of patients. Thus, the sensitivity, specificity, overall accuracy, positive predictive value and negative results amounted to 73.9%, 48.6%, 58.3%, 47.2%, 75% respectively.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Linfocintigrafia , Mamografía/métodos , Terapia Neoadyuvante/métodos , Compuestos de Tecnecio , Adulto , Anciano , Axila , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Esquema de Medicación , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Humanos , Metástasis Linfática/diagnóstico , Linfocintigrafia/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
Analysis of mammoscintigraphy is presented to assess the effectiveness of neoadjuvant polychemotherapy for locally advanced breast cancer. In 90% of patients there is defined conformity of scintigraphy data on the effectiveness of performed polychemotherapy to the results of histologic examination of the postoperative material. The sensitivity of scintigraphy in assessing the effectiveness of neoadjuvant polychemoterapy was 83.3%, specificity--87.9%, accuracy--86.3%, predictive value of positive and negative results-78.9% and 90.1%, respectively. Mammoscintigraphy is an effective method to control the response of locally advanced breast cancer to neoadjuvant polychemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Cintigrafía , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
The absolute sensitivity signs of breast cancer to the drug have not yet been developed. Data from clinical trials on the study of experimental laboratory predictive markers of chemosensitivity: TOP2alpha (topoisomerase 2-alpha), beta-tubulin (subunit of dimeric protein tubulin), and BRCA1 (breast cancer 1) are contradictory and not numerous. Analysis of the results by the end of the clinical trial will allow examining the correlation between the effectiveness of preoperative taxane-chemotherapy and the level of experimental and standard molecular markets that is important for development of algorithm of treatment tactics for patients with locally advanced breast cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Adulto , Anciano , Antígenos de Neoplasias/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/cirugía , ADN-Topoisomerasas de Tipo II/análisis , Proteínas de Unión al ADN/análisis , Esquema de Medicación , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Preoperatorio , Taxoides/administración & dosificación , Resultado del Tratamiento , Tubulina (Proteína)/análisisRESUMEN
Having used hematoxylin as a stain, some features of silkworm embryo chromatin in diapause have been studied in normal and parthenogenetic development. With found direct correlation between the number of interphase chromatin grains and the number of chromosomes in the nucleus, we examined cell polyploidization in the embryo at diapause stage. Polyploidization by parthenogenesis is not reducible to endomitotic doubling of the chromosome set because it comprises 6n-nuclei. Explanation of more diverse range of polyploid cells in parthenogenesis needs to consider the fusion of cleavage nuclei that is carried out by the cytoplasmic karyogamic mechanism in the absence of fertilization. For the first time on squash preparations, in diapausing embryo, we have identified primary germ cells (PGC) that are characterized by less compact chromatin, especially in the zygotic form of development, a larger size of the nucleus and cytoplasm, and irregular number and size of nucleoli. Evaluation of PGC ploidy in parthenogenesis by calculation of "loose" chromatin grains in diapause is possible and testifies polyploidization in embryo germ-line. This explains the inevitable admixture of tetraploid eggs in diploid parthenoclone grain and its absence in normal development. Cytological method used has revealed a spiral arrangement of chromatin grains on the inner surface of the nucleus at different levels of ploidy.
Asunto(s)
Bombyx/ultraestructura , Cromatina/ultraestructura , Metamorfosis Biológica/fisiología , Partenogénesis , Animales , Bombyx/embriología , Núcleo Celular/ultraestructura , Cromosomas/ultraestructura , Citoplasma/ultraestructura , Embrión no Mamífero , Femenino , Fertilización/fisiología , Hematoxilina , Histocitoquímica , Interfase/fisiología , Masculino , Microscopía , Óvulo/fisiología , Óvulo/ultraestructura , Poliploidía , TemperaturaRESUMEN
The efficiencies of modern intravenous anesthetics, analgesics, and hypnotics (dormicum, diprivan, ketamine, and fentanyl) in various combinations for artificial abortions was evaluated. Hemodynamic parameters, autonomic status, and clinical signs of awakening were evaluated. The most effective protection was attained with a combination of diprivan, dormicum, and fentanyl.
Asunto(s)
Aborto Inducido , Anestesia , Analgésicos/administración & dosificación , Anestésicos Intravenosos/administración & dosificación , Quimioterapia Combinada , Femenino , Hemodinámica , Humanos , Hipnóticos y Sedantes/administración & dosificación , EmbarazoRESUMEN
At anaphase-telophase I of meiosis in mouse, porcine and bovine oocytes matured in vitro, "eliminatory chromatin" stained by acetohaematoxylin was found. The transformation of this structure was observed to early metaphase II stage by microscopic analysis. The origin and the nature of the "eliminatory chromatin" are discussed.
Asunto(s)
Cromatina/ultraestructura , Meiosis , Oocitos/ultraestructura , Anafase , Animales , Bovinos , Técnicas de Cultivo de Célula/métodos , Separación Celular , Células Cultivadas , Femenino , Ratones , Oocitos/crecimiento & desarrollo , Porcinos , TelofaseAsunto(s)
Contaminación de Equipos , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/etiología , Refrigeración/efectos adversos , Yersiniosis/etiología , Yersinia enterocolitica/patogenicidad , Yersinia/patogenicidad , Desinfección/métodos , Contaminación de Equipos/prevención & control , Enfermedades Transmitidas por los Alimentos/prevención & control , Humanos , Refrigeración/instrumentación , Temperatura , Yersinia/aislamiento & purificación , Yersiniosis/prevención & control , Yersinia enterocolitica/aislamiento & purificaciónRESUMEN
Instrumental methods of investigation were used for the demonstration of changes in the fatty acid composition of F. tularensis, strain 15 Gaiskii, during cultivation in solid culture medium, storage after lyophilization, as well as changes in the functioning of the system of membrane-dependent enzymes of the respiratory chain and in the permeability of cell wall membranes by water molecules and NADH after lyophilization. A relationship between the survival rate of F. tularensis cells after lyophilization and stimulation of their endogenic respiration with NADH and succinate was revealed. An increase in residual moisture from 6 to 10-12% was found to intensify the process of lipid peroxidation during the storage of lyophilized F. tularensis cells of strain 15 Gaiskii.
Asunto(s)
Francisella tularensis/citología , Vacunas Bacterianas , Técnicas Bacteriológicas , Membrana Celular/fisiología , Membrana Celular/ultraestructura , Permeabilidad de la Membrana Celular/efectos de los fármacos , Medios de Cultivo , Francisella tularensis/inmunología , Francisella tularensis/fisiología , Liofilización/instrumentación , Liofilización/métodos , NAD/farmacocinética , Factores de Tiempo , Agua/metabolismoRESUMEN
Effect of temperature shock treatments (0 and 37 degrees C) in early ontogenesis on recombination frequency was studied in two strains of Drosophila X1 and X2. Recombination frequency under treatment with temperature of 0 degrees C and 37 degrees C (shock treatment), as well as at 14 degrees C and 29 degrees C nonshock treatment was found to be dependent on strain genotype, the chromosomal segments under consideration, developmental stage and the age of individuals analysed. Shock treatments usually increase recombination frequency, whereas nonshock treatments lead to unstable and variable recombination frequencies. A concept of ontogenic homeostasis of recombination has been introduced. It is assumed that the effect of temperature treatments on recombination frequency is indirect--i.e. physiologically mediated.
Asunto(s)
Intercambio Genético , Drosophila melanogaster/genética , Recombinación Genética , Animales , Cromosomas , Genotipo , TemperaturaRESUMEN
A spreading technique was used to prepare synaptonemal complexes from animals (Bombyx mori and Mus musculus spermatocytes) and plants (Zea mays microsporocytes). Suspension of hypotonically treated cells was spread over plastic-coated slides and air-dried. Fixed and phosphotungsten acid-stained spread preparations were studied by phase-contrast and electron microscopes. The spreading-through-drying method is more efficient and thereby more preferable as compared to the classical hypophase spreading technique.
Asunto(s)
Desecación/métodos , Meiosis , Complejo Sinaptonémico , Animales , Bombyx , Fraccionamiento Celular , Masculino , Ratones , Microscopía Electrónica/métodos , Microscopía de Contraste de Fase/métodos , Espermatocitos/ultraestructura , Coloración y Etiquetado/métodos , Zea maysRESUMEN
The antigen activity of bile of rabbits, sheep and cattle infected with F. hepatica was investigated by the immunodiffusion methods. The sera obtained from animals with experimental fasciolosis and other infections were used. At the experimental fasciolosis and intensive natural infection antigens were found in bile, one of which was present in all the animals and turned to be identical immunologically to the specific protein antigene (molecular weight is 27 500) isolated from the extract of F. hepatica. Titres of this antigene in bile depended usually on the infection intensity and were, as a rule, higher than titres of corresponding antibodies in the blood serum. The presence of this antigen in bile can serve as a diagnostic indication of fasciolosis especially when ovoscope or immunological methods based on the finding of antibodies are inefficient.
Asunto(s)
Antígenos/análisis , Bilis/inmunología , Epítopos/análisis , Fasciola hepatica/inmunología , Fascioliasis/diagnóstico , Animales , Bovinos , Enfermedades de los Bovinos/diagnóstico , Inmunodifusión/métodos , Masculino , Peso Molecular , Conejos , Ovinos , Enfermedades de las Ovejas/diagnósticoRESUMEN
The proliferative activity of gastric mucous cells (GMC) was studied in white mice following the administration of acetylsalicylic acid (200 mg/kg). One hour before sacrifice all the animals received intraperitoneal injection of 3H-thymidine. The mitotic index and index of labeling nuclei were calculated by means of radioautographers 3, 10 and 20 days after administering the drug. Following 3-day exposure to acetylsalicylic acid the proliferative activity of GMC remained unchanged as compared to controls. Long-term administration (10 and 20 days) of the drug produced no increase in the number of erosions, but there was a statistically significant rise in the proliferative activity of GMC. This rise was accounted for by increased number of proliferating cells in the foveated and cervical divisions of the glands as well as due to the extension of the zone of distribution of precursor cells in the gastric glands as far as the basal divisions. These changes may be considered as manifestation of the protective-adaptive reaction of the gastric mucosa in response to the damaging effect of acetylsalicylic acid.
Asunto(s)
Aspirina/efectos adversos , Mucosa Gástrica/efectos de los fármacos , Animales , División Celular/efectos de los fármacos , Células Epiteliales , Epitelio/efectos de los fármacos , Mucosa Gástrica/citología , Masculino , Ratones , Factores de TiempoRESUMEN
As a result of investigations of the functional acitivty of eukaryote cells damaged by ionizing radiation and alkylating mutagens under conditions of extreme loading, the authors have suggested that natural aging and aging accelerated by mutagens are based on a process of accumulation of functional genetic damages. The molecular nature of these damages differs from the mutational changes and repairable damages of DNA.