RESUMEN
OBJECTIVE: To investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and treatment of primary neuroendocrine tumor (NET) of the testis. METHODS: Using light microscopy and immunohistochemistry, we studied 7 cases of primary NET of the testis, reviewed relevant literature, and analyzed the clinical manifestations, histomorphologic and immunohistochemical characteristics, treatment and prognosis of the tumor. RESULTS: The 7 male patients, at the mean age of 40.6 years, all presented with testicular painless masses, none accompanied with carcinoid syndrome. Histologically, the uniform tumor cells were arranged in trabecular, island, solid and/or flake structures and locally in a tubulo glandular pattern, round and polygonal in shape, with a small amount of lipid vacuoles in the eosinophilic cytoplasm. The cells had round nuclei with fine chromatin and rarely identified mitosis. Immunohistochemical staining showed that the tumor cells were positive for Syn, CgA, NSE and CK, with a Ki-67 positive rate of < 2%. CONCLUSION: Primary NET of the testis is a rare and low-grade malignancy. Early diagnosis and surgical resection are essential for good prognosis. Immunohistochemistry helps its diagnosis and differential diagnosis from other metastatic neuroendocrine carcinoma, teratomas with carcinoid, seminoma, and Sertoli cell tumor.
Asunto(s)
Tumores Neuroendocrinos/patología , Neoplasias Testiculares/patología , Adulto , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patología , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico , Pronóstico , Neoplasias Testiculares/diagnósticoRESUMEN
Histone methyltransferase KMT2D is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL) and has been identified as an important pathogenic factor and prognostic marker. However, the biological relevance of KMT2D mutations on tumor microenvironment remains to be determined. KMT2D mutations were assessed by whole-genome/exome sequencing (WGS/WES) in 334 patients and by targeted sequencing in 427 patients with newly diagnosed DLBCL. Among all 761 DLBCL patients, somatic mutations in KMT2D were observed in 143 (18.79%) patients and significantly associated with advanced Ann Arbor stage and MYC expression ≥ 40%, as well as inferior progression-free survival and overall survival. In B-lymphoma cells, the mutation or knockdown of KMT2D inhibited methylation of lysine 4 on histone H3 (H3K4), downregulated FBXW7 expression, activated NOTCH signaling pathway and downstream MYC/TGF-ß1, resulting in alterations of tumor-induced regulatory T cell trafficking. In B-lymphoma murine models established with subcutaneous injection of SU-DHL-4 cells, xenografted tumors bearing KMT2D mutation presented lower H3K4 methylation, higher regulatory T cell recruitment, thereby provoking rapid tumor growth compared with wild-type KMT2D via FBXW7-NOTCH-MYC/TGF-ß1 axis.
Asunto(s)
Proteína 7 que Contiene Repeticiones F-Box-WD , Linfoma de Células B Grandes Difuso , Mutación , Proteínas Proto-Oncogénicas c-myc , Linfocitos T Reguladores , Humanos , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Animales , Ratones , Femenino , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Masculino , Linfocitos T Reguladores/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Receptores Notch/metabolismo , Persona de Mediana Edad , Línea Celular Tumoral , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Transducción de Señal , Adulto , Progresión de la Enfermedad , AncianoRESUMEN
Many factors are considered to contribute to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), including products of HBV, HBV integration and mutation, and host susceptibility. HBV X protein (HBx) can interfere with several signaling pathways associated with cell proliferation and invasion, and HBx C-terminal truncation has been suggested to impact the development of HCC. This review focuses on the pathological functions of HBx in HBV-induced hepatocarcinogenesis. As a transactivator, HBx can affect regulatory non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs. HBx is also involved in epigenetic modification and DNA repair. HBx interacts with various signal-transduction pathways, such as the p53, Wnt, and nuclear factor-κB pathways. We conclude that HBx hastens the development of hepatoma.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Transducción de Señal , Transactivadores/genética , Transactivadores/metabolismo , Animales , Carcinoma Hepatocelular/virología , Movimiento Celular , Proliferación Celular , Metilación de ADN , Reparación del ADN , Humanos , Neoplasias Hepáticas/virología , MicroARNs/genética , ARN no Traducido/genética , Proteínas Reguladoras y Accesorias ViralesRESUMEN
Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been reported to have anti-inflammatory and antioxidant activity. This study was designed to evaluate the inhibitory effects of pinocembrin on inflammatory mediators production in LPS-stimulated BV2 microglial cells. The results showed that pinocembrin dose-dependently inhibited LPS-induced inflammatory mediators TNF-α, IL-1ß, NO and PGE2 production. Pinocembrin also inhibited LPS-induced iNOS and COX-2 expression. Moreover, pinocembrin inhibited LPS-induced PI3K, Akt phosphorylation, and NF-κB activation, which were required for inflammatory mediators production. Furthermore, treatment of pinocembrin induced nuclear translocation of Nrf2 and expression of HO-1. In conclusion, our data indicated that pinocembrin inhibited LPS-induced inflammatory mediators production by suppressing PI3K/Akt/NF-κB signaling pathway.