RESUMEN
Circulating miR-181а and miR-25, which reflect regulation of the expression of carcinogenesis-related genes, were assayed in patients with invasive carcinoma of no specific type (ICNT) or benign breast diseases (BBDs) and in subjects without pathologies of the mammary gland (controls). miR-181а expression level proved to be higher compared to control in patients with fibroadenoma and adenosis with low, but not high, risk of malignant transformation, as well as in patients with luminal HER2-negative type B (Lum B HER2-), HER2-positive type (HER2+), and triple-negative breast cancer (TNBC) than in the controls and luminal-type (Lum A) breast cancer. MiR-25 expression level prevailed in patients with Lum B HER2- compared to control, Lum A, and TNBC patients compared to Lum A. Thus, miR-181а and miR-25 expression levels may be risk indicators of malignant transformation in some patients with BBD, whereas in patients with ICNT, these levels reflect pathological processes of different directions within the tumor.
Asunto(s)
Neoplasias de la Mama , MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores de Tumor/metabolismoRESUMEN
Differences in the production of cytokines by tumor biopsy specimens were revealed depending on the pathological prognostic stages of The American Joint Committee on Cancer (AJCC) of invasive nonspecific breast carcinoma (INBC). The patients with a predominant absence of metastases in combination with a triple negative molecular subtype differ from the patients with other pathological prognostic stages in the cytokine-producing tumor resource of IL-18, IL-1ß, IL-1Ra, TNF-α, GM-CSF, and MCP-1.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Citocinas/biosíntesis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Humanos , Estadificación de Neoplasias , PronósticoRESUMEN
The study was carried out on samples of invasive breast carcinoma of no special type from 36 patients aged 48.0 to 62.8 years. The effect of HLDF on nonspecific invasive breast carcinoma was a decrease in the relative content of low-differentiated cells and an increase in the relative content of highly differentiated cells. HLDF did not have a cytotoxic effect leading to the death of low-differentiated cells but promoted promotes the acquisition of a higher degree of differentiation by them. A more pronounced effect of HLDF was observed in more aggressive metastasizing forms of neoplasia, which allows us to consider this differentiation factor as a candidate for use in the differentiation therapy of malignant neoplasms.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Proteínas de Neoplasias/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Diferenciación Celular/efectos de los fármacos , Femenino , Humanos , Técnicas In Vitro , Persona de Mediana Edad , Mitosis/efectos de los fármacos , Clasificación del Tumor , Técnicas de Cultivo de ÓrganosRESUMEN
The material of patients with invasive carcinoma of no special type (ICNT) and nonmalignant diseases (ND) of the mammary gland was studied. When comparing the concentrations of histidine-rich glycoprotein (HRG) and E-cadherin (CDH1), statistically significant differences between ICNT and ND by HRG in the supernatant of blood cells and its spontaneous production by biopsies and by CDH1 at its induced production, as well as by influence indices of polyclonal activators on the production of CDH1 were found. When comparing the expression of immunohistochemical markers, no statistically significant differences between ICNT and ND were obtained.
Asunto(s)
Antígenos CD/metabolismo , Neoplasias de la Mama/metabolismo , Mama/metabolismo , Cadherinas/metabolismo , Proteínas/metabolismo , Biomarcadores de Tumor/metabolismo , Biopsia , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , InmunohistoquímicaRESUMEN
The article focuses on the influence of human leukemia differentiation factor (HLDF), carcinoembryonic antigen (CEA), and polyclonal activators (PA) on cytokine production by peripheral blood cells in breast cancer and benign breast diseases. It was found that the influence of internal factors on the production of cytokines by the peripheral blood cells is associated with lymphatic metastasis (CEA: IL-10; HLDF: IL-6, IL-1ß, TNF-α, and G-CSF). One special circumstance was that there were no differences between the production of cytokines by peripheral blood cells in the patients with breast cancer compared to the patients with benign breast diseases with a high risk of malignant transformation. This is evidence of the functional similarity of peripheral blood cells in patients with these conditions. Cytokine production under the influence of PA was different only in case of TNF-α in all study groups.
Asunto(s)
Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Citocinas/sangre , Biomarcadores de Tumor/sangre , Femenino , Humanos , Interleucina-1beta/sangre , Interleucina-6/sangre , Metástasis Linfática , Invasividad Neoplásica , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Biopsy material of patients with malignant and benign breast diseases was examined. HRG mRNA expression was detected in 70% of cases in biopsy material obtained from patients with nonspecific invasive carcinoma and in 66.7% of cases in biopsy material of patients with benign breast diseases. Immunohistochemical analysis revealed expression of collagen II, the beta-1 integrin, and E-cadherin-markers of epithelial-mesenchymal transition. The use of RT-qPCR combined with immunohistochemical study made it possible to identify atypical cells, which can be regarded as precancerous changes, in individual patients.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Neoplasias de la Mama/metabolismo , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/biosíntesis , Proteínas/metabolismo , Adolescente , Adulto , Anciano , Antígenos CD/biosíntesis , Antígenos CD/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Cadherinas/biosíntesis , Cadherinas/genética , Femenino , Humanos , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas/genéticaRESUMEN
The content of mRNA of the histidine-rich glycoprotein (HRG), a potential marker of malignant neoplasia, which can be used in differential diagnosis of breast tumors, was determined in 110 breast tumor biopsy samples. The presence of HRG mRNA did not depend on the cancer type, on the preoperative treatment or its absence, as well as on the tumor progression stage and the presence of metastases.
Asunto(s)
Neoplasias de la Mama/genética , Proteínas/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
We studied effects of nutrient quercetin on cytochromes' Ð 450 1Ð (CYP1A) activities (measured spectrofluorimetrically using 7-ethoxy-resorufin for CYP1A1 and 7-methoxy-resorufin for CYP1A2 as substrates), on mRNA levels (measured by RT-PCR), and on DNA-binding activities (evaluated by an electrophoretic mobility shift assay) of proteins regulating CYP1A expression in untreated and benzo(α)pyrene (BaP)-treated rats. Wistar rats received quercetin, BaP, or both once daily for 1-3 days. Quercetin did not influence CYP1A1 in untreated rats but inhibited BaP-mediated CYP1A induction on the transcriptional level decreasing positive input (AhR functional activity) and increasing negative input (AhRR/ARNT expression and Oct-1 and C/EBP functional activities).
Asunto(s)
Antioxidantes/farmacología , Hidrocarburo de Aril Hidroxilasas/genética , Benzo(a)pireno/toxicidad , Carcinógenos/toxicidad , Mutágenos/toxicidad , Quercetina/farmacología , Animales , Contaminantes Ambientales/toxicidad , Regulación de la Expresión Génica , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
Mechanisms of thioredoxin peroxidase secretion by Opisthorchis felineus were studied in vivo and in vitro. Specific antibodies were obtained and used for western blotting and immunohistochemical detection in Syrian hamster model of opisthorchiasis. Secreted thioredoxin peroxidase protein was accumulated in the worm incubation medium under conditions of oxidative stress and in bile duct cells of hamsters with chronic opisthorchiasis.
Asunto(s)
Anticuerpos/aislamiento & purificación , Conductos Biliares/parasitología , Proteínas del Helminto/metabolismo , Opistorquiasis/parasitología , Opisthorchis/enzimología , Peroxirredoxinas/metabolismo , Animales , Anticuerpos/química , Conductos Biliares/enzimología , Western Blotting , Clonación Molecular , Modelos Animales de Enfermedad , Escherichia coli/genética , Escherichia coli/metabolismo , Peces/parasitología , Expresión Génica , Proteínas del Helminto/agonistas , Proteínas del Helminto/genética , Peróxido de Hidrógeno/farmacología , Inmunohistoquímica , Mesocricetus/parasitología , Opistorquiasis/enzimología , Opisthorchis/efectos de los fármacos , Opisthorchis/genética , Opisthorchis/aislamiento & purificación , Estrés Oxidativo , Peroxirredoxinas/genética , Conejos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunologíaRESUMEN
Dependence of cytokine pattern in the tumor supernatant obtained after cultivation of biopsy samples-on the patients' age was evaluated among patients with invasive ductal carcinoma of the breast. An increase in VEGF and IL-6 production in a group of younger patients was observed. An increase only in interferon γ concentration was revealed in the supernatants of the tumor after addition of polyclonal activators to the culture medium. This result indicates likely secretion of interferon γ in younger patients. The relation among the production of angiogenic factors by tumor cells, age of the patients, and presence or absence of lymph node metastases shows that in such studies, patients have to be stratified by age.
Asunto(s)
Envejecimiento/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Citocinas/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Anciano , Envejecimiento/patología , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Cytokine production was evaluated in supernatants of cultured tumor cells that were obtained by biopsy of the breast invasive ductal carcinoma (IDC) and breast fibroadenoma (FA) and grown in vitro. In the IDC supernatants, the concentrations of pro-inflammatory (pro-oncogenic) cytokines IL-17, IL-18, and IFNγ and of IL-1 receptor antagonist were significantly higher than in the FA cell supernatants. The concentrations of anti-inflammatory cytokine IL-10 and MCP-1 protein in supernatants of IDC cells were significantly lower than those determined in FA supernatants.
Asunto(s)
Neoplasias de la Mama/inmunología , Carcinoma Ductal de Mama/inmunología , Citocinas/inmunología , Fibroadenoma/inmunología , Mediadores de Inflamación/inmunología , Microambiente Tumoral/inmunología , Fraccionamiento Celular , Femenino , Humanos , Células Tumorales CultivadasRESUMEN
The cytokine-producing potential of blood cells has been studied in the atrophic gastritis-adenoma-adenocarcinoma progression of pathological states of the stomach. It has been revealed that, at the initial stage of carcinogenesis, namely adenoma, immunocompetent cells have the highest cytokine-producing proto-oncogenic potential as compared to both atrophic gastritis, which presents a precancerous condition, and completely formed malignant tumor (gastric adenocarcinoma).
Asunto(s)
Adenocarcinoma/sangre , Adenoma/sangre , Citocinas/sangre , Gastritis Atrófica/sangre , Leucocitos/metabolismo , Proteínas de Neoplasias/sangre , Neoplasias Gástricas/sangre , Femenino , Humanos , MasculinoRESUMEN
The production of cytokines by peripheral blood cells and biopsy specimens of tumors stimulated by polyclonal activators (PAs) was evaluated in 34 patients with invasive ductal breast carcinoma using enzyme-linked immunosorbent assay (ELISA). Positive correlation between the stimulation index of polyclonal activators (SIPA) for IL-18 production by the tumor and the relative content of poorly differentiated cells was revealed. The latter, in turn, was positively correlated with the numbers of normal and pathologic mitoses and the degree of malignancy. Cancer cells can produce IL-18, which is involved in the process of angiogenesis, stimulates invasion and metastasis. Decrease in SIPA for the production of IL-6 and GCSF by peripheral blood cells could serve as an indicator of malignant progression in invasive ductal breast carcinoma.
Asunto(s)
Células Sanguíneas/metabolismo , Carcinoma Ductal de Mama/sangre , Factor Estimulante de Colonias de Granulocitos/genética , Interleucina-18/genética , Interleucina-6/genética , Células Sanguíneas/patología , Carcinogénesis/genética , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patología , Concanavalina A/farmacología , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor Estimulante de Colonias de Granulocitos/sangre , Humanos , Interleucina-18/sangre , Interleucina-6/sangre , Lipopolisacáridos/farmacología , Mitosis/genética , Invasividad Neoplásica/genética , Metástasis de la Neoplasia , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Fitohemaglutininas/farmacologíaRESUMEN
The study examined dynamics of the effect of novel phenol antioxidant preparation 3-(3'-tertbutyl- 4'-hydroxyphenyl)propyl thiosulfonate sodium (TS-13) on expression of antioxidant protection enzymes genes GSTP1 and NQO1 and on the content of protein transcription factors NF-κB and ATF-2 in mouse liver. Expression of GSTP1 gene decreased significantly on days 4 and 7 after per os administration of TS-13 (100 mg/kg), but increased on post-administration day 14. On days 7 and 14 post-administration, expression of NQO1 gene was significantly increased. On day 7, the hepatic content of the phosphorylated form of ATF-2 and two subunits of nuclear factor NF-κB (p50, p65) decreased significantly.
Asunto(s)
Factor de Transcripción Activador 2/genética , Antioxidantes/farmacología , Gutatión-S-Transferasa pi/genética , NAD(P)H Deshidrogenasa (Quinona)/genética , FN-kappa B/genética , Ácidos Tiosulfónicos/farmacología , Factor de Transcripción Activador 2/metabolismo , Administración Oral , Animales , Expresión Génica/efectos de los fármacos , Gutatión-S-Transferasa pi/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , FN-kappa B/metabolismo , Fosforilación , Factores de TiempoRESUMEN
1297C/T polymorphism of CYP4F2 gene was studied in 108 patients with chronic liver diseases. No significant correlation with predisposition to rapid liver cirrhosis was revealed without consideration for cirrhosis etiology (OR=0.93, 95% CI=0.28-2.99, p=0.885). In patients with viral cirrhosis, a tendency to association of 1297T allele genotypes with rapid cirrhosis development was found (OR=6.0, 95% CI=0.28-382.64, p=0.222). At the same time, CYP4F2 1297T allele was associated with mild (Child-Pugh class A-B) cirrhosis (OR=2.9, p=0.044).
Asunto(s)
Ácidos Araquidónicos/metabolismo , Agonistas de Receptores de Cannabinoides/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Endocannabinoides/metabolismo , Cirrosis Hepática/genética , Alcamidas Poliinsaturadas/metabolismo , Adolescente , Adulto , Anciano , Familia 4 del Citocromo P450 , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
Patients with infectious viral or toxic cirrhosis of the liver participated in complex clinical pathomorphological and molecular-genetic study aimed at the search for markers of predisposition to accelerated liver fibrosis, in which the xenobiotic biotransformation system is involved. The results demonstrate association between CYP2D6 (1846G/A) genotype and rapid cirrhosis development and indicate the necessity of studying the mechanisms underlying this association.
Asunto(s)
Citocromo P-450 CYP2D6/genética , Hepatitis B/genética , Hepatitis C/genética , Hepatitis Alcohólica/genética , Cirrosis Hepática/genética , Hígado/patología , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Hepacivirus/fisiología , Hepatitis B/complicaciones , Hepatitis B/patología , Hepatitis B/virología , Virus de la Hepatitis B/fisiología , Hepatitis C/complicaciones , Hepatitis C/patología , Hepatitis C/virología , Hepatitis Alcohólica/complicaciones , Hepatitis Alcohólica/patología , Heterocigoto , Homocigoto , Humanos , Hígado/enzimología , Hígado/virología , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Siberia , Población BlancaRESUMEN
Constitutive androstane receptor (CAR, NR1I3), which is under consideration in this review, is a member of the superfamily of nuclear receptors. However, certain features distinguish CAR from the variety of nuclear receptors. First, this receptor has structural features that allow it to display constitutive activity in the absence of a ligand and to interact in a species-specific manner with a huge number of ligands diverse in chemical structure and origin. Second, recently many researchers are focused on CAR because the significance is increasingly shown of its influence on a variety of physiological functions, such as gluconeogenesis, metabolism of xenobiotics, fatty acids, bilirubin, and bile acids, hormonal regulation, etc. In addition to the fundamental scientific interest, the study of CAR is of practical importance because changes in CAR activity can lead to disorders in physiological processes, which finally can result in changes in pathological states. However, despite intensive studies, many mechanisms are still unclear, which makes it difficult to understand the role of CAR in the overall picture of molecular regulation of physiological processes. This review analyzes the features and diversity of the functions of CAR.
Asunto(s)
Terapia Molecular Dirigida , Receptores Citoplasmáticos y Nucleares/metabolismo , Xenobióticos/metabolismo , Animales , Receptor de Androstano Constitutivo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Inactivación Metabólica , Ligandos , Estructura Terciaria de Proteína , Receptores Citoplasmáticos y Nucleares/química , Receptores Citoplasmáticos y Nucleares/genética , Especificidad de la EspecieRESUMEN
Association of CYP2E1 polymorphism with ALT activity increase was studied in patients with pulmonary tuberculosis receiving therapy by intermittent and daily protocols. The greatest increment of ALT activity in the group receiving therapy by intermittent protocol was seen in the patients with CYP2E1*7632TA genotype. In patients with wild homozygotic 1C/1C (6/6) genotype, ALT activity significantly increased, but remained within the normal range (p=0.048). In the group on daily regimen, activity of ALT increased significantly in patients with all genotypes identified. A more pronounced elevation surpassing the median of the upper threshold of ALT norm was observed in patients with 7632TA genotype (p=0.0051) and in patients with 7632TA or -71GT or 1C/1D genotypes in combinations with wild type alleles by other detected polymorphisms (p=0.0277). Detection of the CYP2E1 gene 7632T
Asunto(s)
Alanina Transaminasa/metabolismo
, Citocromo P-450 CYP2E1/genética
, Polimorfismo Genético/genética
, Tuberculosis Pulmonar/enzimología
, Tuberculosis Pulmonar/genética
, Antituberculosos/uso terapéutico
, Genotipo
, Humanos
, Tuberculosis Pulmonar/tratamiento farmacológico
RESUMEN
We studied the effect of BSA (in the isolation medium) on the oxidation rate of succinate, glutamate, pyruvate, and α-ketoglutarate by mitochondria of the brain and liver from C57Bl/6g mice and Taconic Sprague Dawley rats. BSA had no effect on liver mitochondrial respiration, but increased oxidation of substrates (particularly of succinate) in brain mitochondria. Therefore, the major effect of BSA on brain mitochondria is manifested in activation of SDH. The improvement of mitochondrial properties in the brain after treatment with BSA is associated with antioxidant activity of this agent. Our results confirm the hypothesis that inhibition of SDH in brain mitochondria is not the artifact. This process serves as a mechanism protecting neurons from free oxygen radicals during succinate oxidation.
Asunto(s)
Encéfalo/metabolismo , Respiración de la Célula/efectos de los fármacos , Hígado/metabolismo , Mitocondrias/metabolismo , Albúmina Sérica Bovina/farmacología , Animales , Ácido Glutámico/metabolismo , Ácidos Cetoglutáricos/metabolismo , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Ácido Pirúvico/metabolismo , Ratas , Ratas Sprague-Dawley , Ácido Succínico/metabolismoRESUMEN
The relationship between the content of supernatant cytokines and the expression of non-specific type of markers of epithelial-mesenchymal transition markers in the presence (group II) and the absence of lymphogenous metastasis (group I) were studied in biopsy specimens of mammary invasive breast carcinoma. The concentrations of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ß and IL-1Ra, as well as the expression of immunohistochemical (IHC) markers of the epithelial-mesenchymal transition - cadherin-E (CDH1), ß-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that patients of these groups statistically significantly differed in spontaneous production of IL-18 and G-CSF, in terms of the index of the effect of the polyclonal activator on G-CSF production. There was a correlation between the parameter of CII expression in tumor tissue and the production of cytokines by tumor biopsy specimens; it was characteristic of all patients with invasive carcinoma of a non-specific type, and correlations, both direct and reverse between the expression indices of CDH1, CD29 and cytokine production varied depending on the presence or the absence of lymphogenous metastasis. The study revealed the features of the correlation between the production of cytokines by the tumor, its microenvironment and the expression of IHC markers of the epithelial-mesenchymal transition in patients with invasive non-specific breast carcinoma in the presence and absence of lymphogenous metastasis.