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The as-extruded (EX) Mg-Gd-Y alloy studied here exhibited a bimodal structure, composed of fine dynamic recrystallized (DRXed) grains with random orientations and longitudinal coarse hot-worked grains. The slip analysis showed the DRXed grains exhibited mainly basal slips, while the hot-worked grains exhibited mainly prismatic slips during the tensile deformation. The distribution of geometrically necessary dislocations (GNDs) showed that there was strain partitioning between the fine and coarse grain regions. The hetero-deformation induced (HDI) hardening occurred between the two domains. It improves the strength and strain hardening capability of the alloy, leading to good strength-ductility synergy. Microcracks tended to nucleate at the DRXed grain boundaries, as well as at the interface between the two domains. The calculation of geometric compatibility parameter (m') indicated that strain incompatibility between the adjacent grains induced the crack nucleation. The toughening effect of the fine DRXed grains hindered the crack propagation. However, the major crack formed at the interface between the two domains propagated unstably, due to the high stress concentration and the large crack size, causing the final failure.
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Magnesium and magnesium-based alloys are widely used in the transportation, aerospace and military industries because they are lightweight, have good specific strength, a high specific damping capacity, excellent electromagnetic shielding properties and controllable degradation. However, traditional as-cast magnesium alloys have many defects. Their mechanical and corrosion properties cause difficulties in meeting application requirements. Therefore, extrusion processes are often used to eliminate the structural defects of magnesium alloys, and to improve strength and toughness synergy as well as corrosion resistance. This paper comprehensively summarizes the characteristics of extrusion processes, elaborates on the evolution law of microstructure, discusses DRX nucleation, texture weakening and abnormal texture behavior, discusses the influence of extrusion parameters on alloy properties, and systematically analyzes the properties of extruded magnesium alloys. The strengthening mechanism is comprehensively summarized, the non-basal plane slip, texture weakening and randomization laws are comprehensively summarized, and the future research direction of high-performance extruded magnesium alloys is prospected.
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Cell division cycle associated 8 (CDCA8) is a component of the chromosomal passenger complex and plays an essential role in mitosis, meiosis, cancer growth, and undifferentiated state of embryonic stem cells. However, its expression and role in adult tissues remain largely uncharacterized. Here, we studied the CDCA8 transcription in adult tissues by generating a transgenic mouse model, in which the luciferase was driven by a 1-kb human CDCA8 promoter. Our previous study showed that this 1-kb promoter was active enough to dictate reporter expression faithfully reflecting endogenous CDCA8 expression. Two founder mice carrying the transgene were identified. In vivo imaging and luciferase assays in tissue lysates revealed that CDCA8 promoter was highly activated and drove robust luciferase expression in testes. Subsequently, immunohistochemical and immunofluorescent staining showed that in adult transgenic testes, the expression of luciferase was restricted to a subset of spermatogonia that were located along the basement membrane and positive for the expression of GFRA1, a consensus marker for early undifferentiated spermatogonia. These findings for the first time indicate that the CDCA8 was transcriptionally activated in testis and thus may play a role in adult spermatogenesis. Moreover, the 1-kb CDCA8 promoter could be used for spermatogonia-specific gene expression in vivo and the transgenic lines constructed here could also be used for recovery of spermatogonia from adult testes.
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Espermatogonias , Testículo , Masculino , Humanos , Adulto , Ratones , Animales , Testículo/metabolismo , Espermatogonias/metabolismo , Espermatogénesis/genética , Ratones Transgénicos , Luciferasas/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismoRESUMEN
Al-Si-Cu-Mg cast aluminum alloys have important applications in automobile lightweight due to their advantages such as high strength-to-weight ratio, good heat resistance and excellent casting performance. With the increasing demand for strength and toughness of automotive parts, the development of high strength and toughness Al-Si-Cu-Mg cast aluminum alloys is one of the effective measures to promote the application of cast aluminum alloys in the automotive industry. In this paper, the research progress of improving the strength and toughness of Al-Si-Cu-Mg cast aluminum alloys was described from the aspects of multi-component alloying and heat treatment based on the strengthening mechanism of Al-Si-Cu-Mg cast aluminum alloys. Finally, the development prospects of automotive lightweight Al-Si-Cu-Mg cast aluminum alloys is presented.
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The medium carbon steel warm deformation was carried out in a Gleeble-3500 simulator, and the microstructure was observed on a scan electron microscopy (SEM) and optical microscope (OM). The results show that the dynamic reversal transformation (DRT) of austenite occurred during the multipass deformation at a temperature of 675 °C. The austenite grain size is about 3.4 µm at the stain of 2.67. The thermodynamics was discussed based on the stress activation model. The critical stress of DRT is in the range of 265.94-294.28 MPa, which is related to the Schmit factor, without considering the distortion energy. Meanwhile, the submicron ferrite was obtained after the air cooling stage. The texture of the ultrafine ferrite possessed the characteristics of good, deep drawing properties.
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The nuclear reactor pressure vessel is an important component of a nuclear power plant. It has been used in harsh environments such as high temperature, high pressure, neutron irradiation, thermal aging, corrosion and fatigue for a long time, which puts forward higher standards for the performance requirements for nuclear pressure vessel steel. Based on the characteristics of large size and wall thickness of the nuclear pressure vessel, combined with its performance requirements, this work studies the problems of forging technology, mechanical properties, irradiation damage, corrosion failure, thermal aging behavior and fatigue properties, and summarizes the research progress of nuclear pressure vessel materials. The influencing factors of microstructures evolution and mechanism of mechanical properties change of nuclear pressure vessel steel are analyzed in this work. The mechanical properties before and after irradiation are compared, and the influence mechanisms of irradiation hardening and embrittlement are also summarized. Although the stainless steel will be surfacing on the inner wall of nuclear pressure vessel to prevent corrosion, long-term operation may cause aging or deterioration of stainless steel, resulting in corrosion caused by the contact between the primary circuit water environment and the nuclear pressure vessel steel. Therefore, the corrosion behavior of nuclear pressure vessels materials is also summarized in detail. Meanwhile, the evolution mechanism of the microstructure of nuclear pressure vessel materials under thermal aging conditions is analyzed, and the mechanisms affecting the mechanical properties are also described. In addition, the influence mechanisms of internal and external factors on the fatigue properties, fatigue crack initiation and fatigue crack propagation of nuclear pressure vessel steel are analyzed in detail from different perspectives. Finally, the development direction and further research contents of nuclear pressure vessel materials are prospected in order to improve the service life and ensure safe service in harsh environment.
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Objectives: The study aimed to evaluate the diagnostic performance of optical coherence tomography (OCT) in identifying functionally significant coronary stenosis in a vessel with single stenosis. Background: The OCT-based morphofunctional computational method for deriving the optical flow ratio (OFR) has diagnostic value, as it can identify the functional severity of coronary stenosis, but the ability of the OFR to aid the OCT in determining coronary stenosis hemodynamics in single-stenosis lesion remains unclear. Methods: 74 vessels with single stenosis were studied in 69 patients; all cases were performed through OCT and quantitative flow ratio (QFR), and OCT images were used to perform OFR. Results: Among vessels with single stenosis, OFR showed a good correlation with QFR (r = 0.86; p < 0.001). Taking QFR as the standard, the vessel-level diagnosis accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of OFR were 90% (95% CI: 81 to 96), 94% (95% CI: 77 to 99), 88% (95% CI: 74 to 96), 85% (95% CI: 68 to 94) and 95% (95% CI: 82 to 99), respectively. Among vessels with OFR/QFR concordance, both the minimum lumen area (MLA) and minimum lumen diameter (MLD) showed excellent diagnostic efficiency (MLA: area under the curve (AUC) = 0.92, 95% CI: 0.85 to 0.98, p < 0.001; MLD: AUC = 0.93, 95% CI: 0.86 to 0.98, p < 0.001) in determining the functional significance of coronary stenosis in a single stenosis lesion, and the best cutoff values were 1.55 mm2 and 1.40 mm. Conclusions: OFR has a good correlation with QFR. OCT-measured MLA and MLD have excellent diagnostic efficiency in identifying the hemodynamic significance of coronary stenosis in a vessel with single stenosis.
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The cell division cycle associated 8 (CDCA8) gene plays an important role in mitosis. Overexpression of CDCA8 was reported in some human cancers and is required for cancer growth and progression. We found CDCA8 expression was also high in human ES cells (hESCs) but dropped significantly upon hESC differentiation. However, the regulation of CDCA8 expression has not yet been studied. Here, we characterized the CDCA8 promoter and identified its cis-elements and transcription factors. Three transcription start sites were identified. Reporter gene assays revealed that the CDCA8 promoter was activated in hESCs and cancer cell lines. The promoter drove the reporter expression specifically to pluripotent cells during early mouse embryo development and to tumor tissues in tumor-bearing mice. These results indicate that CDCA8 is transcriptionally activated in hESCs and cancer cells. Mechanistically, two key activation elements, bound by transcription factor NF-Y and CREB1, respectively, were identified in the CDCA8 basic promoter by mutation analyses and electrophoretic motility shift assays. NF-Y binding is positively correlated with promoter activities in different cell types. Interestingly, the NF-YA subunit, binding to the promoter, is primarily a short isoform in hESCs and a long isoform in cancer cells, indicating a different activation mechanism of the CDCA8 transcription between hESCs and cancer cells. Finally, enhanced CDCA8 promoter activities by NF-Y overexpression and reduced CDCA8 transcription by NF-Y knockdown further verified that NF-Y is a positive regulator of CDCA8 transcription. Our study unearths the molecular mechanisms underlying the activation of CDCA8 expression in hESCs and cancer cells, which provides a better understanding of its biological functions.
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Factor de Unión a CCAAT/metabolismo , Proteínas de Ciclo Celular/biosíntesis , Células Madre Embrionarias/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias/metabolismo , Regiones Promotoras Genéticas , Activación Transcripcional , Animales , Factor de Unión a CCAAT/genética , Proteínas de Ciclo Celular/genética , Diferenciación Celular/genética , Embrión de Mamíferos/embriología , Células Madre Embrionarias/patología , Técnicas de Silenciamiento del Gen , Células HeLa , Xenoinjertos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Transgénicos , Trasplante de Neoplasias , Neoplasias/patologíaRESUMEN
To assess the changes in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 expression in breast cancer patients after various neoadjuvant chemotherapies. Data from 138 locally advanced breast cancer patients with histological diagnoses were reviewed. Seventy patients (group 1) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 50 mg/m(2) pirarubicin every 21 days. Sixty-eight patients (group 2) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 75 mg/m(2) docetaxel every 21 days. The biomarker changes of the operated tumor tissues were compared with the initial core biopsies. ER, PR, HER2 and Ki-67 expression changed by 28.6%, 22.9%, 17.1% and 54.3%, respectively, after neoadjuvant chemotherapy in group 1 and 16.2%, 22.1%, 13.2% and 70.6%, respectively, after neoadjuvant chemotherapy in group 2. There were significant differences between the groups regarding ER and Ki-67 status changes, and these changes can be used to inform treatment strategies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Antígeno Ki-67/análisis , Antígeno Ki-67/biosíntesis , Antígeno Ki-67/efectos de los fármacos , Persona de Mediana Edad , Terapia Neoadyuvante , Receptor ErbB-2/análisis , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/efectos de los fármacos , Receptores de Estrógenos/análisis , Receptores de Estrógenos/biosíntesis , Receptores de Estrógenos/efectos de los fármacos , Receptores de Progesterona/análisis , Receptores de Progesterona/biosíntesis , Receptores de Progesterona/efectos de los fármacos , Taxoides/administración & dosificaciónRESUMEN
The present study intended to develop receptor-mediated luciferase reporter gene assays to evaluate and compare the estrogen receptor (ER), androgen receptor (AR) and thyroid hormone receptor (TR) activities of target chemicals. Di-2-ethylhexyl-phthalate (DEHP), chlorpyrifos (CPF), 2,4-dichlorophenoxyacetic acid (2,4-D) and bisphenol A (BPA) are some of the most common contaminants in drinking water and are frequently detected in China and worldwide. The chemicals were tested at concentrations of 0.1, 1, 10 and 100 times their maximum contaminant level in drinking water. The results showed that BPA possessed various activities on ER, AR and TR. DEHP and CPF could suppress 17ß-estradiol or testosterone activity with different potencies, and DEHP possessed weaker anti-thyroid hormone activity. 2,4-D showed no agonist or antagonist activity against these hormone receptors, but it significantly enhanced the activity of testosterone through AR. Furthermore, the mixture of DEHP and CPF exhibited stronger ER and AR antagonist activities than each single component alone, but their combined effects were less than the expected effects based on the additive model. These results implied that the transcription activation mediated by hormone receptors was the potential endocrine-disrupting mechanism of the test chemicals. Our study also provided useful tools for evaluation of their endocrine disrupting activity.
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Agua Potable/química , Genes Reporteros , Contaminantes Químicos del Agua/toxicidad , Ácido 2,4-Diclorofenoxiacético/análisis , Ácido 2,4-Diclorofenoxiacético/toxicidad , Animales , Compuestos de Bencidrilo , China , Chlorocebus aethiops , Cloropirifos/análisis , Cloropirifos/toxicidad , Dietilhexil Ftalato/análisis , Dietilhexil Ftalato/toxicidad , Agua Potable/análisis , Disruptores Endocrinos/toxicidad , Estradiol/genética , Luciferasas/genética , Luciferasas/metabolismo , Fenoles/análisis , Fenoles/toxicidad , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Hormona Tiroidea/genética , Receptores de Hormona Tiroidea/metabolismo , Testosterona/genética , Testosterona/metabolismo , Células Vero , Contaminantes Químicos del Agua/análisisRESUMEN
ERBB2/HER2/NEU, a member of the epidermal growth factor receptor family, is overexpressed in more than 25 % of non-small cell lung cancer and is considered to be a significant and independent prognostic factor in lung cancer. Here we generated a lung specific HER2 overexpressing transgenic mouse model. In this model, HER2 was driven by the human surfactant protein-C promoter to investigate the role of the HER2 oncogene in pulmonary carcinogenesis and progression. Notably, significant pathological changes, including lymphocyte infiltration and mesenchymal cells hyperplasia, were found in the lung tissue of transgenic mice aged from 4 to 12 months. The occurrence and severity of those lesions increased as the mice aged. Some inflammatory factors, such as tumor necrosis factor, interleukin 1 and interleukin 6, were upregulated in lung tissue of transgenic mice compared with that of wild-type mice, implying that long-term HER2 overexpression could induce serious lung inflammation and some precancerous lesions. This model would be useful for studying the mechanism of HER2 involvement in lung carcinogenesis and for understanding the relationship between carcinogenesis and inflammation.
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Transformación Celular Neoplásica/genética , Neumonía/genética , Receptor ErbB-2/genética , Animales , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Orden Génico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Transgénicos , Neumonía/patología , Receptor ErbB-2/metabolismoRESUMEN
Nicotine is a natural alkaloid produced by tobacco plants, and the mechanisms of its catabolism by microorganisms are diverse. In the present study, we reported the mutation, cloning, and identification of two novel genes involved in nicotine degradation from the newly isolated Pseudomonas sp. strain HZN6. Transposon mutagenesis identified a HZN6 mutant in which the nicotine-degrading pathway was blocked at pseudooxynicotine. A 3,874-bp DNA fragment flanking the transposon insertion site was obtained through self-formed adaptor PCR. Two open reading frames (designated pao and sap) were analyzed, and the deduced amino acid sequences shared 29% identity with 6-hydroxy-l-nicotine oxidase from Arthrobacter nicotinovorans and 49% identity with an aldehyde dehydrogenase from Bartonella henselae. Both pao and sap were cloned and functionally expressed in recombinant Escherichia coli BL21. The pao gene encoded a novel pseudooxynicotine amine oxidase with noncovalently bound flavin adenine dinucleotide (FAD) and exhibited substrate specificity removing the methylamine from pseudooxynicotine with the formation of 3-succinoylsemialdehyde-pyridine and hydrogen dioxide. The sap gene encoded a NADP(+)-dependent 3-succinoylsemialdehyde-pyridine dehydrogenase that catalyzed the dehydrogenation of 3-succinoylsemialdehyde-pyridine to 3-succinoyl-pyridine. Genetic analyses indicated that the pao gene played an essential role in nicotine or pseudooxynicotine mineralization in strain HZN6, whereas the sap gene did not. This study provides novel insight into the nicotine-degrading mechanism at the genetic level in Pseudomonas spp.
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Genes Bacterianos , Monoaminooxidasa/metabolismo , Nicotina/metabolismo , Pseudomonas/enzimología , Succinato-Semialdehído Deshidrogenasa (NADP+)/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Butanonas/metabolismo , Clonación Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Flavina-Adenina Dinucleótido/metabolismo , Metilaminas/metabolismo , Datos de Secuencia Molecular , Monoaminooxidasa/genética , Nicotina/análogos & derivados , Pseudomonas/clasificación , Pseudomonas/genética , Pseudomonas/metabolismo , Piridinas/metabolismo , Succinato-Semialdehído Deshidrogenasa (NADP+)/genéticaRESUMEN
A novel nicotine-degrading Pseudomonas sp. strain, HZN6, was isolated from a pesticide-wastewater treatment facility in Hangzhou. The strain could grow on nicotine as its sole source of carbon, nitrogen, and energy. The strain's main intermediate metabolites were determined to be pseudooxynicotine, 3-succinoyl-pyridine (SP), and 6-hydroxy-3-succinoyl-pyridine (HSP). A Tn5 transposon mutant was generated in which the degradation pathway was blocked at the SP. A 4,583-bp DNA fragment flanking the transposon insertion site was obtained through self-formed adaptor PCR and analyzed. The mutant gene orfC displays 89% deduced amino acid sequence identity with the sirA-like gene (sirA2, a sulfurtransferase homologue gene) of Pseudomonas stutzeri A1501. The orfC-disrupted strain lost the ability to degrade SP, and the complementation strains with the orfC from the Pseudomonas sp. HZN6 and the sirA2 (PP_1233) from Pseudomonas putida KT2440 recovered the degradation ability. Though the orfC-disrupted strain also lost the xanthine dehydrogenase activity, the effects of tungsten on the degradation of SP and hypoxanthine revealed that the hydroxylation of SP to HSP was not a xanthine dehydrogenase type. These results demonstrated that the orfC gene was essential for the SP metabolism involved in the nicotine metabolic pathway in the Pseudomonas sp. HZN6 strain. This study might advance the understanding of the nicotine metabolic mechanism in Pseudomonas.
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Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Nicotina/metabolismo , Pseudomonas/metabolismo , Piridinas/metabolismo , Aguas del Alcantarillado/microbiología , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Biodegradación Ambiental , Datos de Secuencia Molecular , Filogenia , Pseudomonas/clasificación , Pseudomonas/genética , Pseudomonas/aislamiento & purificación , Alineación de SecuenciaRESUMEN
PURPOSE: The basal-like phenotype has been found to be an independent poor prognostic factor for breast cancer. The aim of this study was to evaluate the association of WW domain-containing oxidoreductase (WWOX) expression with the basal-like subtype and clinicopathological parameters and to determine the prognostic significance of WWOX expression in patients with breast cancer. METHODS: Immunohistochemical analysis of WWOX expression was performed on 267 breast carcinoma samples, and then the mean value of WWOX expression was correlated to the basal-like status and clinicopathological parameters of the samples. The prognostic value of WWOX in primary breast cancer patients was determined for disease-free survival and overall survival. RESULTS: Expression of WWOX was negative in 29% of cases, and mean WWOX levels were significantly lower in basal-like breast cancers than in those of the non-basal-like subtype (P = 0.01). WWOX negativity was associated with decreased disease-free survival (DFS) (hazard ratio = 1.83; 95% CI, 1.01 to 3.28), but not with overall survival. Other tumor variables that showed a significant association with patient survival times included node status (hazard ratio = 0.38; 95% CI, 0.17 to 0.85) and breast cancer phenotype (hazard ratio = 0.36; 95% CI, 0.19 to 0.68). Multivariate regression analysis showed that lymph node involvement (hazard ratio = 0.43; 95% CI, 0.19 to 0.97) and basal-like subtype (hazard ratio = 0.33; 95% CI, 0.17 to 0.63) were also significant independent prognostic variables, and WWOX expression was of borderline significance for DFS (hazard ratio = 0.56; 95% CI, 0.31 to 1.03). CONCLUSIONS: Reduced WWOX expression is associated with the basal-like subtype and a poor disease-free survival rate for breast cancer patients. Additional studies are warranted to better understand the role of WWOX expression, to further refine prognosis, and to optimize treatment in patients with basal-like breast cancer.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Carcinoma Basocelular/química , Oxidorreductasas/análisis , Proteínas Supresoras de Tumor/análisis , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Basocelular/genética , Carcinoma Basocelular/patología , Factores de Confusión Epidemiológicos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Tamaño de la Muestra , Oxidorreductasa que Contiene Dominios WWRESUMEN
To evaluate the associations of phosphorylated c-Jun NH2-terminal kinase (p-JNK) expression with clinicopathological features in patients with papillary thyroid carcinoma, p-JNK expression were immunohistochemically measured in 121 thyroid samples. p-JNK was overexpressed in papillary thyroid carcinomas with respect to matched nontumorous tissues (P=0.000), which was supported by western blot analysis. Increased p-JNK expression was significantly associated with the presence of lymph node metastases (P=0.001) and advanced TNM stages (P=0.02). Furthermore, p-JNK expression was positively correlated with osteopontin (OPN) expression (r=0.58, P<0.001). Activation of p-JNK may play a role in the carcinogenesis and lymph node metastasis of papillary thyroid carcinoma, and may be a molecular target for therapeutic intervention.
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Carcinoma Papilar/enzimología , Proteínas Quinasas JNK Activadas por Mitógenos/biosíntesis , Neoplasias de la Tiroides/enzimología , Carcinoma Papilar/patología , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Osteopontina/metabolismo , Fosforilación , Neoplasias de la Tiroides/patologíaRESUMEN
RATIONALE AND OBJECTIVES: Mammography contributes to the improvement of breast carcinoma survival through early detection and treatment of breast lesions. The basal-like phenotype has been found to be an independent poor prognostic factor for breast cancer. The aim of this study was to determine the mammographic correlates of the basal-like phenotype of invasive breast cancer, and to more precisely predict patient outcome and those individuals who will be responsive to a specific therapeutic regimen. MATERIALS AND METHODS: The mammographic findings in 267 patients with operable breast cancer were correlated with the basal-like subtype identified using immunohistochemical assessment of breast cancer cases, including estrogen receptor, progesterone receptor, HER-2/neu status, cytokeratin (CK5/6), and epidermal growth factor receptor. RESULTS: Of the 267 invasive breast cancers, 40 (15%) were of the basal-like phenotype. Basal-phenotype tumors were significantly more likely to manifest as a mass (P = .002), most of which were indistinct margin (P =.035), at mammography, and architecture distortion at mammography (P = .002). CONCLUSION: The mammographic appearances of basal-like tumors, more mass and architecture distortion, suggest more rapid carcinogenesis. Additional studies are warranted to further refine prognosis, and to optimize treatment in patients with basal-like breast cancer.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Carcinoma Basocelular/diagnóstico por imagen , Carcinoma Basocelular/patología , Mamografía , Tomografía Computarizada por Rayos X , Adulto , Anciano , Biomarcadores de Tumor/análisis , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como AsuntoRESUMEN
PURPOSE: To evaluate the osteopontin (OPN) protein expression levels in breast carcinomas to determine if they correlate with mammographic appearances such as calcifications. MATERIALS AND METHODS: This retrospective study was institutional review board approved. Informed consent was obtained from patients. Clinical history, histopathologic findings, mammographic features, and OPN expression as determined with immunohistochemistry results were evaluated in 141 women with breast cancer. The median age of patients was 53 years (range, 29-82 years). Mammographic features and clinicopathologic characteristics were correlated with tumor OPN expression. chi(2) And Fisher exact tests were used to evaluate the association of OPN expression with mammographic and clinicopathologic features. RESULTS: Calcifications on mammograms (P = .012), spiculated margins of mass on mammograms (P = .02), "triple-negative" (ie, cancer that is estrogen receptor, progesterone receptor, and human epidermal growth factor receptor negative) phenotype (P = .02), and lymph node metastasis (P < .0001) were significantly associated with OPN status. In contrast to OPN-negative tumors, OPN-positive tumors were more likely to have spiculated margins (57.6% vs 9.2%), to be associated with calcifications (54.3% vs 30.6%), to be a triple-negative phenotype (26% vs 8.1%), and to have axillary lymph node metastasis (81.5% vs 38.8%). Most calcifications were of pleomorphic morphology (60.4% vs 11.8%, P = .046). CONCLUSION: OPN could play a role in the formation of calcifications that often are associated with breast cancer.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Calcinosis/diagnóstico por imagen , Calcinosis/metabolismo , Osteopontina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Distribución de Chi-Cuadrado , Femenino , Humanos , Técnicas para Inmunoenzimas , Mamografía , Persona de Mediana Edad , Invasividad Neoplásica , Fenotipo , Estudios RetrospectivosRESUMEN
Basal-like carcinomas and human epidermal growth factor receptor 2 (HER-2/neu) overexpression carcinomas are the subgroups of breast cancers that have the most aggressive clinical behavior. Phosphorylation/activation of c-Jun NH2-terminal kinase is characterized as a stress-activated protein kinase, which regulates apoptosis after cellular stress. The aim of this study was to evaluate the association of phosphorylated c-Jun NH2-terminal kinase expression with phenotypes and clinicopathologic parameters of breast cancer. Phosphorylated c-Jun NH2-terminal kinase was immunohistochemically measured in a cohort of 160 patients with invasive breast cancer treated with therapeutic surgery followed by anthracycline or docetaxel-based chemotherapy. These results were further correlated with the phenotypes and clinicopathologic characteristics of breast cancers. Increased phosphorylated c-Jun NH2-terminal kinase expression was significantly associated with lack of estrogen receptor expression (P < .0001), positivity for cytokeratins 5/6 (P = .029), epidermal growth factor receptor (P = .035), basal-like phenotype (P = .015), and "triple-negative" phenotype (P = .01). Furthermore, the positive expression of phosphorylated c-Jun NH2-terminal kinase was positively correlated with p-glycoprotein (r = 0.54, P < .0001) and multidrug resistance-associated protein 1(r = 0.38, P < .0001) but not with lung resistance protein (r = -0.02, P = .78). Our results indicate that the activation of phosphorylated c-Jun NH2-terminal kinase may play a role in the carcinogenesis of basal-like and triple-negative breast carcinoma.
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Adenocarcinoma Mucinoso/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Carcinoma Medular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adenocarcinoma Mucinoso/cirugía , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/cirugía , Carcinoma Medular/cirugía , Distribución de Chi-Cuadrado , Factor de Crecimiento Epidérmico/metabolismo , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Inmunohistoquímica , Queratinas/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Estadificación de Neoplasias , Selección de Paciente , Fosforilación , Regulación hacia Arriba , Partículas Ribonucleoproteicas en Bóveda/metabolismoRESUMEN
The HER-2 proto-oncogene (also called c-erbB-2/neu) encodes the protein, p185, which is closely related to the growth and metastasis of adenocarcinoma, and is overexpressed in 25-30% of human breast cancers. In this study, we attempt to reverse the malignant phenotype of the breast cancer cell line, MCF-7, using a HER-2-specific hammerhead ribozyme. Two anti-HER-2 hammerhead ribozymes, RZ1 and RZ2, were synthesized, inserted separately into the nonviral eukaryotic expression vector, pcDNA3.1(-), and transfected into MCF-7 cells. Analyses showed that the HER-2 mRNA and p185, as well as oncogene k-ras were down-regulated remarkably in the ribozyme-transfected cells, while the onco-suppressor gene, p53, was up-regulated. Furthermore, the tumorigenicity of the RZ1-stably transfected MCF-7 cells was decreased dramatically in nude mice. These results demonstrate that the use of anti-HER-2 ribozymes may be a beneficial strategy for gene therapy of breast cancer.
Asunto(s)
Adenocarcinoma/terapia , Neoplasias de la Mama/terapia , Regulación Neoplásica de la Expresión Génica/genética , Marcación de Gen/métodos , Terapia Genética/métodos , ARN Catalítico/farmacología , Receptor ErbB-2/metabolismo , Animales , Western Blotting , Línea Celular Tumoral , Cartilla de ADN/genética , Femenino , Citometría de Flujo , Vectores Genéticos/genética , Humanos , Ratones , Ratones Desnudos , Proto-Oncogenes Mas , ARN Catalítico/genética , Receptor ErbB-2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TransfecciónRESUMEN
At 14:28 on 12 May 2008, Sichuan Province of China suffered a devastating earthquake measuring 8.0 on the Richter scale with more than 80 000 human lives lost and millions displaced. With inadequate shelter, poor access to health services, and disrupted ecology, the survivors were at enormous risk of infectious disease outbreaks. This work, believed to be unprecedented, was carried out to contain a possible outbreak through onsite monitoring of airborne biological agents in the high-risk areas. In such a mission, a mobile laboratory was developed using a customized vehicle along with state-of-art bioaerosol and molecular equipment and tools, and deployed to Sichuan 11 days after the earthquake. Using a high volume bioaerosol sampler (RCS High Flow) and Button Inhalable Aerosol Sampler equipped with gelatin filters, a total of 55 air samples, among which are 28 filter samples, were collected from rubble, medical centers, and camps of refugees, troops and rescue workers between 23 May and 9 June, 2008. After pre-treatment of the air samples, quantitative polymerase chain reaction (qPCR), gel electrophoresis, limulus amebocyte lysate (LAL) assay and enzyme-linked immunosorbent assay (ELISA) were applied to detect infectious agents and to quantify environmental toxins and allergens. The results revealed that, while high levels of endotoxin (180 approximately 975 ng/m3) and (1,3)-beta-d-glucans (11 approximately 100 ng/m3) were observed, infectious agents such as Bacillus anthracis, Bordetella pertussis, Neisseria meningitidis, Mycobacterium tuberculosis, influenza A virus, bird flu virus (H5N1), enteric viruses, and Meningococcal meningitis were found below their detection limits. The total bacterial concentrations were found to range from 250 to 2.5 x 10(5) DNA copies/L. Aspergillus fumigatus (Asp f 1) and dust mite allergens (Der p 1 and Der f 1) were also found below their detection limits.