We report here that the Id2 (inhibitor of DNA binding 2) gene is a novel target of transcriptional activation by EWS -FLI1 and EWS -ERG, two fusion proteins that characterize Ewing family tumors (EFTs). To identify downstream targets of these EWS -ETS fusion proteins, we introduced EWS -ETS fusion constructs into a human fibrosarcoma cell line by retroviral transduction. cDNA microarray analysis revealed that Id2 expression was up-regulated by introducing the EWS -ETS fusion gene but not by the normal full-length ETS gene. An Id2 promoter-luciferase reporter assay showed that transactivation by EWS -ETS involves the minimal Id2 promoter and may function in cooperation with c-Myc within the full-length regulatory region. A chromatin immunoprecipitation assay revealed direct interaction between the Id2 promoter and EWS-FLI1 fusion protein in vivo. Significantly higher expression of Id2 and c-Myc was observed in all of the six EFT cell lines examined compared to six other sarcoma cell lines. Moreover, high levels of Id2 expression were also observed in five of the six primary tumors examined. Id2 is generally thought to affect the balance between cell differentiation and proliferation in development and is highly expressed in several cancer types. Considering these previous studies, our data suggest that the oncogenic effect of EWS -ETS may be mediated in part by up-regulating Id2 expression.

Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumors (PNETs) are associated with a chromosomal translocation resulting in a fusion of the amino-terminus of EWS with the DNA-binding domain of an ETS transcription factor (most commonly FLI1 or ERG). Although previous reports suggested that these chimera proteins would act as aberrant transcription factors, their downstream targets have not been fully elucidated. To identify downstream targets of these EWS-ETS fusion proteins, we introduced EWS-ETS fusion constructs into a human fibrosarcoma cell line, HT-1080, by retroviral transduction. Here we report that Tenascin-C (TNC) is induced to a significantly higher level in cells expressing EWS-ETSs than in cells expressing normal ETSs. Furthermore, through use of an antisense cDNA expression vector we show that expression of endogenous TNC mRNA and protein were reduced coordinately with attenuation of EWS-FLI1 fusion protein expression. A chromatin immunoprecipitation assay showed direct interaction between the TNC promoter and the EWS-FLI1 fusion protein in vivo. In addition, a luciferase reporter assay revealed that EWS-ETSs upregulated the TNC gene through four ETS binding sites in the TNC promoter. High levels of TNC expression were observed in a subset of ES cell lines (3 of 6) and primary tumors (4 of 6). Together with previous studies showing that TNC expression is involved in the invasive and malignant phenotype of several tumor types, our data suggest that the oncogenic effect of EWS-ETS may be mediated in part by upregulating of TNC expression.

Although associated with a relatively high rate of complications, each reconstruction method is useful, with a high rate of successful limb salvage and a good long-term functional outcome. Cite this article: 2017;99-B:1237-43.

BackgroundTension gastrothorax is a kind of obstructive shock with prolapse and distention of the stomach into the thoracic cavity. Progressive gastric distension leads to mediastinal shift, reduced venous return, decreased cardiac output, and ultimately cardiac arrest. Therefore, it is crucial to decompress the stomach distension for the initial resuscitation of tension gastrothorax.Case presentationA 75-year-old female was transported to our resuscitation bay due to motor vehicle crash. At the time of arrival to our hospital, the patient developed cardiac arrest. While undergoing cardiopulmonary resuscitation, an unstable pelvic ring was recognized, so we performed a resuscitative thoracotomy to control hemorrhage and to perform direct cardiac massage. Once we performed the thoracotomy, the stomach and omentum prolapsed out of the thoracotomy site and through the diaphragm rupture site and spontaneous circulation was recovered. Neither the descending aorta nor the heart was collapsed. Although we had continued the treatment for severe pelvic fracture (including blood transufusions), the patient died. Given that (1) the stomach prolapsed out of the body at the time of the thoracotomy; (2) at the same timing, spontaneous circulation returned; and (3) the descending aorta and heart did not collapse, we hypothesized that the main cause of the initial cardiac arrest was tension gastrothorax.ConclusionsRecognition of tension gastrothorax pathophysiology, which is a form of obstructive shock, makes it possible to manage this injury correctly.

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