RESUMEN
Interdigitating dendritic cell sarcoma (IDCS) is an aggressive neoplasm and is an extremely rare disease, with a challenging diagnosis. Etiology of IDCS is also unknown and most studies with only case reports. In our case, immunohistochemistry showed that the tumor cells were positive for S100, CD45, and CD68, but negative for CD1a and CD21. This study aimed to investigate the causative factors of IDCS by sequencing the protein-coding regions of IDCS. We performed whole-exome sequencing with genomic DNA from blood and sarcoma tissue of the IDCS patient using the Illumina Hiseq 2500 platform. After that, we conducted Sanger sequencing for validation of sarcoma-specific variants and gene ontology analysis using DAVID bioinformatics resources. Through comparing sequencing data of sarcoma with normal blood, we obtained 15 nonsynonymous single nucleotide polymorphisms (SNPs) as sarcoma-specific variants. Although the 15 SNPs were not validated by Sanger sequencing due to tumor heterogeneity and low sensitivity of Sanger sequencing, we examined the function of the genes in which each SNP is located. Based on previous studies and gene ontology database, we found that POLQ encoding DNA polymerase theta enzyme and FNIP1 encoding tumor suppressor folliculin-interacting protein might have contributed to the IDCS. Our study provides potential causative genetic factors of IDCS and plays a role in advancing the understanding of IDCS pathogenesis.
Asunto(s)
Proteínas Portadoras/genética , ADN Polimerasa Dirigida por ADN/genética , Sarcoma de Células Dendríticas Interdigitantes/genética , Sarcoma/genética , Sarcoma de Células Dendríticas Interdigitantes/diagnóstico por imagen , Sarcoma de Células Dendríticas Interdigitantes/patología , Células Dendríticas/metabolismo , Células Dendríticas/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Sarcoma/patología , Secuenciación del Exoma , ADN Polimerasa thetaRESUMEN
A series of styrylheterocycles was prepared and their inhibitory activities against nitric oxide (NO) production were evaluated in a cell culture system using lipopolysaccharide-stimulated RAW264.7 macrophage cells. Our studies have identified a new series of inhibitors on NO production, providing the basis for further development of potent inhibitors. The preliminary structure-activity relationship, to elucidate the essential structural requirements, has been described. Mechanistic studies suggest that the suppression of iNOS mRNA transcription is, at least in part, related to the inhibitory activity of styrylheterocycles.
Asunto(s)
Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Compuestos Heterocíclicos/síntesis química , Compuestos Heterocíclicos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Estirenos/síntesis química , Estirenos/farmacología , Animales , Células Cultivadas , Cartilla de ADN , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Ratones , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Relación Estructura-ActividadRESUMEN
Resveratrol analogs were newly synthesized and evaluated for cytotoxicity in cultured human lung and colon cancer cells. 3,5,4-Trimethoxy-trans-stilbene and 3,5,2',4'-tetramethoxy-trans-stilbene were found to be more potent rather than resveratrol. 3,4,5-Trimethoxy-4'-bromo-cis-stilbene was the most active among the test compounds.