RESUMEN
OBJECTIVE: The aim: Was to study the state of the nitric oxide system, LPO and antioxidant system in the body of experimental animals in simulated metabolic syndrome. The aim of the study was to study the state of the nitric oxide system, lipid peroxidation and antioxidant system in the body of experimental animals in simulated MS. PATIENTS AND METHODS: Materials and methods: The study was performed on 20 white male Wistar rats. Male control rats (n = 10) were fed a normal control diet. Male rats of the main group (n = 10) were fed a diet high in fat (over 60 % energy from fats) for 16 weeks, thus modeling the development of MS. The indicators of the prooxidant and antioxidant system, as well as the nitric oxide system were determined by photospectrographic method. RESULTS: Results: In animals with simulated MS, intensification of lipoperoxidation (statistically significantly higher level of TBA-active products 1.84 times), depletion of antioxidant protection (statistically significantly lower level of superoxide dismutase 2 times), activation of nitric oxide system (statistically significantly higher NO-synthase level 2.15 times) were found compared with intact animals. CONCLUSION: Conclusions: In animals with simulated MS, activation of lipid peroxidation processes, depletion of antioxidant protection and increased.
Asunto(s)
Síndrome Metabólico , Animales , Animales de Laboratorio/metabolismo , Antioxidantes , Humanos , Peroxidación de Lípido , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Ratas , Ratas WistarRESUMEN
We report that human secretory breast carcinoma (SBC), a rare subtype of infiltrating ductal carcinoma, expresses the ETV6-NTRK3 gene fusion previously cloned in pediatric mesenchymal cancers. This gene fusion encodes a chimeric tyrosine kinase with potent transforming activity in fibroblasts. ETV6-NTRK3 expression was confirmed in 12 (92%) of 13 SBC cases, but not in other ductal carcinomas. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary epithelial cells resulted in transformed cells that readily formed tumors in nude mice. Phenotypically, tumors produced glands and expressed epithelial antigens, confirming that EN transformation is compatible with epithelial differentiation. This represents a recurrent chromosomal rearrangement and expression of a dominantly acting oncogene as a primary event in human breast carcinoma.
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Fusión Artificial Génica , Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Proteínas de Unión al ADN/genética , Receptor trkC/genética , Proteínas Represoras/genética , Células 3T3 , Adolescente , Adulto , Anciano , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Niño , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 15 , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-ets , Receptor trkC/química , Receptor trkC/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Represoras/química , Proteínas Represoras/metabolismo , Retroviridae/genética , Translocación Genética , Proteína ETS de Variante de Translocación 6RESUMEN
Previous studies of the PAX3-FKHR and PAX7-FKHR gene fusions in alveolar rhabdomyosarcoma (ARMS) indicated that the corresponding fusiontranscripts are not detectable in 20% of ARMS cases. To investigate the genetic features of this ARMS subset, we identified 23 ARMS cases in which PAX3-FKHR and PAX7-FKHR transcripts were not detected by a standard sensitivity reverse transcription-PCR (RT-PCR) assay. Subsequent analysis with a high sensitivity RT-PCR assay identified low-level expression of PAX3-FKHR or PAX7-FKHR in three cases. Analysis with a Southern blot assay for PAX3 and PAX7 rearrangements and a fluorescence in situ hybridization assay for FKHR rearrangements identified three cases with variant fusions in which PAX3 or PAX7 is postulated to be joined to novel genomic loci. In one such case, RT-PCR analysis of candidate partners identified a fusion of PAX3 to AFX, which is highly similar in structure and function to FKHR. Additional fluorescence in situ hybridization analysis identified two cases in which a PAX3-FKHR or PAX7-FKHR genomic fusion is present but is not associated with a fusion transcript detectable by RT-PCR. Finally, our analyses of the PAX3, PAX7, and FKHR loci did not identify rearrangements in >50% of cases, consistent with the possibility that there is a true fusion-negative subset. In summary, our analysis of ARMS cases without characteristic PAX3-FKHR or PAX7-FKHR transcripts identified several genetically distinct subsets including low expression or atypical presentation of standard fusions, variant fusions with other genes, and possibly true fusion-negative cases.
Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas de Homeodominio/genética , Proteínas de Fusión Oncogénica/genética , Rabdomiosarcoma Alveolar/genética , Factores de Transcripción/genética , Secuencia de Bases , Southern Blotting , Proteínas de Ciclo Celular , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead , Reordenamiento Génico , Heterogeneidad Genética , Humanos , Hibridación Fluorescente in Situ , Datos de Secuencia Molecular , Factor de Transcripción PAX3 , Factor de Transcripción PAX7 , Factores de Transcripción Paired Box , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Increased expression of the transcription/translation regulatory protein Y-box binding protein-1 (YB-1) is associated with cancer aggressiveness, particularly in breast carcinoma. Here we establish that YB-1 levels are elevated in invasive breast cancer cells and correlate with reduced expression of E-cadherin and poor patient survival. Enforced expression of YB-1 in noninvasive breast epithelial cells induced an epithelial-mesenchymal transition (EMT) accompanied by enhanced metastatic potential and reduced proliferation rates. YB-1 directly activates cap-independent translation of messenger RNAs encoding Snail1 and other transcription factors implicated in downregulation of epithelial and growth-related genes and activation of mesenchymal genes. Hence, translational regulation by YB-1 is a restriction point enabling coordinated expression of a network of EMT-inducing transcription factors, likely acting together to promote metastatic spread.