RESUMEN
Background and Objectives: We aimed to investigate the role of Wnt2 expression in colorectal cancer (CRC) prognosis and evaluate its potential as a therapeutic target in BRAF-mutated CRC. Materials and Methods: Exactly 136 samples of formalin-fixed paraffin-embedded CRC tissue specimens were obtained from patients who underwent surgical resection for CRC. The gene mutation status of the samples was detected using fluorescence PCR. Wnt2 expression was detected using immunohistochemistry. Survival curves with high Wnt2 expression and BRAF mutations were compared using the Kaplan-Meier method. A nomogram was constructed to determine the estimated overall survival probability. We also predicted the 3-year and 5-year survival rates for patients with high Wnt2 expression and BRAF mutations. In total, 50 samples of BRAF-mutated CRC were collected and detected Wnt2 expression by immunohistochemistry. The Chi-squared test was used to analyze the association between Wnt2 expression and BRAF-mutated CRC. Results: High Wnt2 expression and BRAF mutations are associated with poor prognosis of CRC. Multivariate survival analyses indicated that high Wnt2 expression and BRAF mutations are significant independent predictors of CRC prognosis. Furthermore, high Wnt2 expression was significantly associated with BRAF-mutated CRC, and Wnt2 may be a potential therapeutic target for BRAF-mutated CRC. Conclusions: High Wnt2 expression confers poor prognosis in colorectal cancer and represents a novel therapeutic target in BRAF-mutated CRC.
Asunto(s)
Neoplasias Colorrectales , Proteína wnt2 , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Mutación , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Análisis de Supervivencia , Proteína wnt2/genéticaRESUMEN
B7-H3 (CD276), an immune checkpoint molecule, is aberrantly overexpressed in many types of cancer, and plays important roles in tumor immune evasion, carcinogenesis and metastasis, as well as angiogenesis. However, the mechanisms underlying B7-H3-promoted angiogenesis are still largely unknown. In this study, based on the observation of overexpression of B7-H3 on the tumor cells and vascular endothelial cells (VECs) in colorectal cancer (CRC) tissues, we investigated the roles of cancer cell-drived exosomal B7-H3 in tumor angiogenesis and metastasis through crosstalk between cancer cells and VECs. We found that CRC cell-drived exosomal B7-H3 was uptaken by human umbilical vein endothelial cells (HUVECs) and consequently activated the AKT serine/threonine kinase 1 (AKT1) / mechanistic target of rapamycin kinase (mTOR) / vascular endothelial growth factor A (VEGFA) signaling pathway, thus augmenting the abilities of migration, invasion and tube formation of HUVECs. Furthermore, administration of CRC cell-drived exosomes with reinforced B7-H3 promoted the pulmonary angiogenesis and metastasis of CRC cells in mice. In addition, high expression of B7-H3 was observed in urinary exosomes isolated from CRC patients. Our findings reveal that CRC-derived exosomal B7-H3 promotes tumor angiogenesis and metastasis by activating the AKT1/mTOR/VEGFA signaling pathway. It provides novel insights into the roles of CRC-drived exosomes in CRC progression.
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Neoplasias Colorrectales , MicroARNs , Humanos , Animales , Ratones , Factor A de Crecimiento Endotelial Vascular/metabolismo , Neoplasias Colorrectales/patología , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Patológica/metabolismo , Línea Celular Tumoral , Proliferación Celular , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Antígenos B7/metabolismoRESUMEN
The preparation of lightweight aggregate (LWA) by high-temperature sintering is a promising method for recycling solid waste safely, especially for solidifying heavy metals effectively. The main aim of this research was to systematically evaluate the effects of the flux components on LWA, including Na2O, MgO, CaO, and Fe2O3. The physical properties and chromium solidification mechanism of LWA were characterized and analyzed. The results showed that the addition of Na facilitated LWA preparation and Cr solidification, whereas Ca, Mg, and Fe were deleterious to some extent. Further analysis indicated that increasing the Fe2O3 content was not conducive to the reduction of Cr because its decomposition reaction creates an oxygen-rich environment. The results of this research could provide a meaningful guide for regulating the composition of raw materials for the production of LWA to treat industrial Cr-containing solid waste.
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Metales Pesados , Aguas del Alcantarillado , Calor , Metales Pesados/análisis , Reciclaje , Residuos SólidosRESUMEN
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating central nervous system disease with time and space disseminated lesions that usually occurs in young adults, typically aged between 20 and 45 years. Recently, researches have indicated MS may be associated with increased risk of fracture and osteoporosis. In this review, we aim to identify the fracture risk in MS patients, also address the pathogenic mechanisms and interventions of fracture in those patients.
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Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Esclerosis Múltiple/complicaciones , Osteoporosis/epidemiología , Osteoporosis/etiología , Bases de Datos Bibliográficas/estadística & datos numéricos , Personas con Discapacidad , Humanos , Esclerosis Múltiple/epidemiología , Osteoporosis/prevención & control , RiesgoRESUMEN
OBJECTIVE: To study the changes in humoral immunological function and their clinical significance in cerebral hemorrhage. METHODS: Among 115 cases of cerebral hemorrhage, there was low volume bleeding in 39 case, middle volume in 37 cases, and large volume in 39 cases. The ratios of CD19+-CD25+ and CD19+-CD25-B lymphocytes were determined by flow cytometry, and the content of IgA, IgG, IgM, and complement C3 were determined with scattered turbidimetry. The changes in humoral immunological function were compared in patients with different degrees of hemorrhage, and their variation in acute and recovery stages of disease were respectively assessed. RESULTS: The ratios of CD19+-CD25+and CD19+-CD25-B lymphocyte, and the levels of IgA, IgG, IgM, and C3 were higher than those of controls (all P<0.05). The ratios of CD19+-CD25+ and CD19+-CD25- B lymphocyte, and the contents of IgA, IgG,IgM and C3 were increased with the increase in amount of hemorrhage(all P<0.05). The ratios of CD19+-CD25+ and CD19+-CD25-B lymphocytes in recovery stage were lower than those in acute stage (all P<0.05). CONCLUSION: There are activations of humoral immunological functions in cerebral hemorrhage. The more abundant in hemorrhage and the severer in disease, the more predominant in the changes in humoral immunological functions.