RESUMEN
We herein report a rare case of early oesophageal cancer combined with an oesophageal muscularis propria defect discovered under endoscopic submucosal dissection. The surgeon did not damage the muscularis propria during endoscopic resection; however, we observed the mediastinal cavity as well as the later occurrence of subcutaneous emphysema. Consequently, the patient was considered to have a muscularis propria defect. This phenomenon has not been reported in the literature to date.
Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Endoscopía , Neoplasias Gástricas/patología , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Colorectal Cancer (CC), a common disease causing approximately million deaths annually, has been the third most frequent type of malignancy. We aimed to identify gene-specific DNA methylation signature to function as prognostic and predictive markers for CC patient survival. METHODS: Expression profiles of gene-specific DNA methylation and the corresponding clinical information of 201 CC patients were downloaded from The Cancer Genome Atlas (TCGA) dataset and differentially expressed gene-specific DNA methylation was identified after tumor subtype classification. A risk score model was further built by analyzing the expression data of these gene-specific DNA methylations from the training dataset of CC patients. RESULTS: Totally, 214 gene-specific DNA methylations were found to be expressed significantly between different subtypes of CC, including 150 up-regulated and 64 down-regulated ones. Up-regulated gene-specific DNA methylation accounted for 70.1% and the down-regulated gene-specific DNA methylation accounted for 29.9%. Hereinto, six gene-specific DNA methylations were obtained, including methy_vimentin and methy_ TFPI2, which were found significantly correlated with overall survival status of patients with CC. CONCLUSIONS: With the six gene-specific DNA methylation signatures, patients in the training set were divided into low-risk and high- risk groups. What's more, gene-specific DNA methylation target genes were highly associated with protein phosphorylation, which indicated that further research on phosphorylation of target gene-coding protein might provide new sight on the treatment of CC.
Asunto(s)
Neoplasias Colorrectales/genética , Metilación de ADN/genética , Predisposición Genética a la Enfermedad , Biomarcadores de Tumor , Regulación hacia Abajo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Regulación hacia ArribaRESUMEN
A growing body of evidence has demonstrated that Eph/ephrin signalling may serve a central role in intestinal diseases. However, whether erythropoietinproducing hepatocellular (Eph)/ephrin signalling is associated with the development of postinfectious irritable bowel syndrome (PIIBS) is still unknown. In the present study, the role of Eph/Ephrin signalling in lipopolysaccharide (LPS)induced intestinal injury was evaluated in vivo and in vitro. LPS treatment significantly increased the levels of proinflammatory mediators [monocyte chemoattractant protein1, tumour necrosis factor α, interleukin (IL)1ß, IL6, intercellular adhesion molecule 1 and vascular cell adhesion molecule1], activated the EphA2Ephrin A1, protein kinase B (Akt)nuclear factor (NF)κB, SrcNFκB and Wnt/ßcatenin signalling pathways, and inhibited EphB1Ephrin B3 signalling in colon tissues, and primary cultured enteric neuronal and glial cells. Notably, EphA2 monoclonal antibody (mAb) treatment or Ephrin B3 overexpression could partially alleviate the LPSinduced upregulation of proinflammatory mediators, and AktNFκB, SrcNFκB and Wnt/ßcatenin signalling pathways. In addition, EphA2 mAb treatment could partially inhibit LPSinduced inactivation of EphBEphrin B3 signalling, while Ephrin B3 overexpression could abrogate LPSinduced activation of EphA2Ephrin A1 signalling. EphB1/Ephrin B3 signalling may antagonise the EphA2/Ephrin A1dependent pathway following LPS treatment. The results associated with the EphA2 signaling pathway, indicated that Eph/ephrin signalling may serve a bidirectional role in LPSinduced intestinal injury. Eph/ephrin signalling may be a novel therapeutic target for LPSinduced intestinal injury and potentially PIIBS.
Asunto(s)
Efrina-A1/metabolismo , Efrina-B3/metabolismo , Mucosa Intestinal/metabolismo , Síndrome del Colon Irritable/metabolismo , Lipopolisacáridos/toxicidad , Receptor EphA2/metabolismo , Receptor EphB1/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Intestinos/lesiones , Intestinos/patología , Síndrome del Colon Irritable/inducido químicamente , Síndrome del Colon Irritable/patología , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Though the detailed pathological mechanism of post-infectious irritable bowel syndrome (PI-IBS) remains unclear, accumulating evidence indicates that oxidative stress and inflammation are implicated in the process of PI-IBS. Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. EphA2, a member of Eph receptor family, promotes oxidative stress and inflammatory responses via regulation of Nrf2 and NF-κB signaling pathways in various types of human diseases. Understanding the mechanisms by which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for the development of new strategies to treat PI-IBS. However, the effects of ALW-II-41-27, a novel EphA2 inhibitor on PI-IBS and the underlying molecular mechanisms have never been studied. In the present study, we showed that ALW-II-41-27 decreased gastrointestinal motility and abdominal withdrawal reflex (AWR) scores, markedly reduced the levels of oxidative stress markers [4-hydroxy-2-nonenal (4-HNE), protein carbonyl, and 8-hydroxy-2-de-axyguanine (8-OHdG)] and proinflammatory cytokines (TNF-α, IL-6, IL-17, and ICAM-1), and remarkably increased the level of anti-inflammatory cytokine (IL-10) in serum and colon of Trichinella spiralis-infected mice. Moreover, ALW-II-41-27 was effective in suppressing oxidative stress and inflammation in LPS-treated NCM460 colonic cells. Treatment of ALW-II-41-27 reversed the activation of NF-κB and inactivation of Nrf2 in LPS-treated NCM460 cells. Importantly, these protective effects of ALW-II-41-27 were partially inhibited by EphA2 KO and abolished by EphA2 overexpression. In conclusion, EphA2 may represent a promising therapeutic target for patients with PI-IBS and ALW-II-41-27 might function as a novel therapeutic agent for PI-IBS.