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ABSTRACTStrawberries intended for processing are usually frozen to withstand storage and distribution. However, freezing and thawing can cause the degradation of bioactive compounds. The aim of this study was to determine the optimal conditions for frozen storage and thawing to minimize any loss of nutrients prior processing. Different freezing treatments (−20°C, shock-freezing with liquid nitrogen, −80 °C) up to 6 months of storage and thawing treatments (4°C, room temperature, 37°C, microwave) were compared based on the content of organic acids, sugars, and phenolic compounds as well as the activity of peroxidase and polyphenol oxidase. During frozen storage at −20°C over 6 months, the sucrose content decreased by 59%, but only a 17% loss of ascorbic acid was observed, and no significant loss of anthocyanins was detected. However, more significant changes in composition were detected after thawing. When thawed at 4°C for 24 h, ascorbic acid content decreased by 32%, anthocyanin content by 30%, and sucrose content by 66%. Based on our study, the frozen storage caused smaller changes in the fruit’s composition than thawing. From the thawing procedures, the microwave thawing showed minimal changes in the composition of strawberries.

This investigation aimed to identify the most favorable cultivar based on plant metabolites for potential targeted cultivation in the pharmaceutical industry. The analysis revealed the presence of 19 individual phenolics and 80 individual volatiles across the cultivars, a breadth of data not previously explored to such an extent. Flavones emerged as the predominant phenolic group in all mint-scented cultivars, except for peppermint, where hydroxycinnamic acids dominated. Peppermint exhibited high concentrations of phenolic acids, particularly caffeic acid derivatives and rosmarinic acid, which are known for their anti-inflammatory and antioxidant properties. Luteolin-rich concentrations were found in several mint varieties, known for their antioxidative, antitumor, and cardio-protective properties. Swiss mint and spearmint stood out with elevated levels of flavanones, particularly eriocitrin, akin to citrus fruits. Monoterpene volatiles, including menthol, camphor, limonene, and carvone, were identified across all cultivars, with Swiss mint and spearmint exhibiting the highest amounts. The study underscores the potential for targeted cultivation to enhance volatile yields and reduce agricultural land use. Notably, chocolate mint demonstrated promise for volatile content, while apple mint excelled in phenolics, suggesting their potential for broader agricultural, pharmaceutical, and food industry production.

Secondary metabolites, namely, phenolic and volatile organic compounds, contribute to the nutritional and organoleptic quality of the strawberry fruit. This study focuses on the changes in the content of phenolic compounds and volatile organic compounds during the ripening, from green to overripe fruit, of five strawberry cultivars (‘Asia’, ‘CIVN 766’, ‘Aprica’, ‘Clery’, and ‘Malwina’). Additionally, these changes are compared with the colour of the fruit and peroxidase and polyphenol oxidase activity. Our results show that the accumulation of secondary metabolites (phenolic and volatile organic compounds) significantly changed during the ripening process for all of the studied cultivars. As for phenolic compounds, flavanols and hydroxybenzoic acid derivatives comprised between 87 and 95% of the total phenolic compound content in unripe green fruit. In contrast, anthocyanins and hydroxycinnamic acid derivatives comprised between 64 and 77% of the total phenolic compound content in overripe fruit, except in the fruit of the cultivar ‘CIVN766’. When it comes to the aroma profile, the content of aldehydes decreased by 24–49% as the fruit ripened, and the accumulation of esters increased. Our study also shows that the ripening process differs among cultivars, and it is therefore necessary to define ripening indicators separately for each cultivar.

Abstract The advent of dose intensified interval compressed therapy has improved event-free survival for patients with localized Ewing sarcoma (EwS) to 78% at 5 years. However, nearly a quarter of patients with localized tumors and 60–80% of patients with metastatic tumors suffer relapse and die of disease. In addition, those who survive are often left with debilitating late effects. Clinical features aside from stage have proven inadequate to meaningfully classify patients for risk-stratified therapy. Therefore, there is a critical need to develop approaches to risk stratify patients with EwS based on molecular features. Over the past decade, new technology has enabled the study of multiple molecular biomarkers in EwS. Preliminary evidence requiring validation supports copy number changes, and loss of function mutations in tumor suppressor genes as biomarkers of outcome in EwS. Initial studies of circulating tumor DNA demonstrated that diagnostic ctDNA burden and ctDNA clearance during induction are also associated with outcome. In addition, fusion partner should be a pre-requisite for enrollment on EwS clinical trials, and the fusion type and structure require further study to determine prognostic impact. These emerging biomarkers represent a new horizon in our understanding of disease risk and will enable future efforts to develop risk-adapted treatment.

The aim of our study was to determine how the content and composition of volatile organic compounds (VOCs) change with crossbreeding. We included three autochthonous Slovenian species of roses (R. pendulina, R. spinosissima, and R. gallica) and several cultivars derived from them in the research. The results were compared with the content of the reference plant R. damascena, which is known worldwide for its rich VOC profile and is used in the perfume industry. We found that the total VOC content ranged from 2.579 µg/g FW (‘Fruhlingsmorgen’) to 168.24 µg/g FW (‘Violacea’). According to the content of total VOCs, the variety ‘Charles de Mills’ (43.12 µg/g DM) was the most similar to the variety R. damascena (44.55 µg/g DM). We can conclude that the flowers of the roses we included in the study are a rich source of VOCs. VOC content in hybrids varies depending on the purpose and goals of breeders. We also found that flowering time had no effect on VOC content and composition. With this study, we not only carefully examined the VOC profile of roses but also clearly showed which compounds were present in individual taxa. In this way, it is possible to select a suitable variety or cultivar depending on the desired use, for example, for flavoring food or for a floral fragrance in the perfume industry.

Black fruits, especially blackberries and black currants, are highly appreciated by consumers due to their nutraceutical properties, which have reported health benefits. This study aimed to assess the fruit quality of the blackberry (cv. ‘Čačanska Bestrna’) and black currant (cv. ‘Čačanska Crna’) created at the Fruit Research Institute, Čačak (Republic of Serbia) by evaluating basic quality parameters (fruit weight, soluble solids), and content of primary (sugars and organic acids) and secondary (phenolic compounds) metabolites. Additionally, the study examined the quality of frozen and long-term frozen storage (6, 9, and 12 months). The results showed that ‘Čačanska Crna’ contained a high level of total soluble solids (15.23°Bx), sugars (93.06 mg g−1), and a high index of sweetness (159.48) as well as a high content of acids (34.35 mg g−1) in the fruit. Both species were found to contain forty-seven phenolic compounds, including phenolic acids, flavanols, and anthocyanins, analyzed using high performance liquid chromatography-mass spectrometry (HPLC-MS). ‘Čačanska Bestrna’ had the highest amounts of phenolic acids (66.85 mg 100 g−1) and flavanols (53.99 mg 100 g−1), whereas ‘Čačanska Crna’ showed the highest levels of flavonols (8.57 mg 100 g−1) and anthocyanins (139.11 mg 100 g−1). Furthermore, the study revealed that anthocyanins were the most abundant phenolic group in both blackberries and black currants, and their levels remained constant during frozen storage. The sugar content in both species remained unchanged, while the acid concentration increased over time in blackberries but remained consistent in black currants. Overall, the findings highlight the superior phenolic content, particularly anthocyanins, of the cultivars with black fruits selected in Serbia. These cultivars have great commercial potential for the fresh market and processing. Moreover, the study suggests that frozen storage is an effective method for preserving their quality and beneficial properties.

Summary: Ewing sarcoma (EwS) is a highly aggressive tumor of bone and soft tissues that mostly affects children and adolescents. The pathognomonic oncofusion EWSR1::FLI1 transcription factor drives EwS by orchestrating an oncogenic transcription program through de novo enhancers. By integrative analysis of thousands of transcriptomes representing pan-cancer cell lines, primary cancers, metastasis, and normal tissues, we identify a 32-gene signature (ESS32 [Ewing Sarcoma Specific 32]) that stratifies EwS from pan-cancer. Among the ESS32, LOXHD1, encoding a stereociliary protein, is the most highly expressed gene through an alternative transcription start site. Deletion or silencing of EWSR1::FLI1 bound upstream de novo enhancer results in loss of the LOXHD1 short isoform, altering EWSR1::FLI1 and HIF1α pathway genes and resulting in decreased proliferation/invasion of EwS cells. These observations implicate LOXHD1 as a biomarker and a determinant of EwS metastasis and suggest new avenues for developing LOXHD1-targeted drugs or cellular therapies for this deadly disease.

The distribution of primary and secondary metabolites within a fruit can affect its nutritional and organoleptic quality, as fruit can vary in size and shape. This study investigated the differences in the distribution of the primary and secondary metabolites in the fruit of four strawberry cultivars (‘Asia’, ‘Clery’, ‘Frederica’, and ‘Sandra’) that were collected at one harvest point. The study included an analysis of the individual sugars, organic acids, phenolic compounds, and enzymes responsible for the degradation of phenolics. All of the studied cultivars showed a lower pH, higher total organic acid content, and lower glucose and fructose content in the outer part of the fruit. Differences were also observed in the total phenolic and anthocyanin contents, which were always higher in the outer part. The absolute differences in the total phenolic content ranged from 3723 to 6154 mg kg−1 dry weight. Our results provide a basis for understanding the differences in the biosynthesis of these metabolites within this fruit and prove that it is essential to mix samples well before extractions to obtain results that are representative of the whole fruit.

This study was conducted to estimate the yield, and to identify and quantify primary and secondary metabolites in fruit of Malus domestica Borkh. cv. ‘Sampion’ under two agrotechnical factors: the floor management (herbicide fallow and living mulch) and the dose of nitrogen (50, 80, 110, and 140 kg ha−1). Compared to herbicide fallow, living mulch did not decrease yield. Research showed a rich composition of phenolic and volatile organic compounds in apples, which varied with the evaluated factors, as well as with the weather conditions during the vegetation season. The precipitation deficit and high summer temperatures did not contribute to proper fruit growth and development and led to a higher content of phenolic compounds in the fruit flesh from trees in herbicide fallow compared to living mulch. Living mulch, which could be a factor regulating the availability of nitrogen to trees, stimulated the synthesis of anthocyanins, which was also potentiated by low average temperatures at harvest time, resulting in a large area of fruit skin red blush.

Strawberries are appreciated by consumers for their characteristic taste and health benefits, which enhance their demand throughout the year. Everbearing strawberries can produce fruits for a longer period and could thus meet this demand, but the fruit quality depends on environmental factors and the cultivar. This study focused on the effect of environmental conditions on the physical attributes and the composition of everbearing Capri cultivar fruit harvested from the end of June to the end of October. A positive correlation was observed between temperature and organic acid content (r = 0.87), and a positive correlation was observed between sunshine duration, anthocyanin (r = 0.87) and phenolic compound contents (r = 0.89). Additionally, the composition of sugars was affected by the environmental conditions. While strawberries harvested towards the end of October, when lower temperatures predominated, were larger in size and had a higher sugar/acid ratio, fruit harvested in the middle of August, when there were longer periods of sunshine, had higher anthocyanin and phenolic compound contents. In conclusion, strawberries with higher sugar/acid ratios are obtained when temperatures are lower, while strawberries exposed to longer periods of sunshine are richer in health-promoting compounds.

Abstract Rhabdoid tumor (RT) is a pediatric cancer characterized by the inactivation of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. Although this deletion is the known oncogenic driver, there are limited effective therapeutic options for these patients. Here we use unbiased screening of cell line panels to identify a heightened sensitivity of rhabdoid tumor to mithramycin and the second‐generation analogue EC8042. The sensitivity of MMA and EC8042 was superior to traditional DNA damaging agents and linked to the causative mutation of the tumor, SMARCB1 deletion. Mithramycin blocks SMARCB1‐deficient SWI/SNF activity and displaces the complex from chromatin to cause an increase in H3K27me3. This triggers chromatin remodeling and enrichment of H3K27ac at chromHMM‐defined promoters to restore cellular differentiation. These effects occurred at concentrations not associated with DNA damage and were not due to global chromatin remodeling or widespread gene expression changes. Importantly, a single 3‐day infusion of EC8042 caused dramatic regressions of RT xenografts, recapitulated the increase in H3K27me3, and cellular differentiation described in vitro to completely cure three out of eight mice.

The consumption of fresh vegetables has been consistently associated with numerous health benefits. However, several factors (such as allelochemicals) influence yield, quality, and metabolites, which inevitably affect the fruit quality and health benefits. The present study was conducted to investigate the yield, quality, metabolic responses, and potential toxicity of Cucumis sativus grown in juglone-containing soils. For the treatments, pure juglone (100 µM, 1 mM) and walnut leaf extracts (100 µM) in soil concentrations found in walnut orchards were used. A total of 36 phenolic compounds were identified and quantified in fruits, leaves, and roots using a mass spectrometer coupled with high-performance liquid chromatography. We concluded that juglone at a concentration of 100 µM or walnut leaf extract at the same juglone concentration does not affect the yield of C. sativus, while juglone at a concentration of 1 mM strongly affects it. In the case of juglone, juglone itself was found only in the roots of C. sativus, but not in the leaves or fruits, so C. sativus fruits are considered safe for cultivation in juglone-containing soils. However, this could prove problematic if the plants grown are tubers or root vegetables. The data suggest that juglone itself inhibits secondary metabolism in the plant, making it more susceptible to stress and pathogen attacks.

EWS/FLI is the defining mutation of Ewing sarcoma. This oncogene drives malignant transformation and progression and occurs in a genetic background characterized by few other recurrent cooperating mutations. In addition, the tumor is absolutely dependent on the continued expression of EWS/FLI to maintain the malignant phenotype. However, EWS/FLI is a transcription factor and therefore a challenging drug target. The difficulty of directly targeting EWS/FLI stems from unique features of this fusion protein as well as the network of interacting proteins required to execute the transcriptional program. This network includes interacting proteins as well as upstream and downstream effectors that together reprogram the epigenome and transcriptome. While the vast number of proteins involved in this process challenge the development of a highly specific inhibitors, they also yield numerous therapeutic opportunities. In this report, we will review how this vast EWS-FLI transcriptional network has been exploited over the last two decades to identify compounds that directly target EWS/FLI and/or associated vulnerabilities.

In the genus Phyteuma, the taxonomic delimitation of some species is difficult since a high variability of morphological traits, such as flower color, is present, probably due to high levels of hybridization. Historic descriptions and the morphological traits used in the taxonomic keys are sometimes unclear and lead to misinterpretations. Here, a detailed analysis of flower color variability in different populations of sympatric P. spicatum, P. ovatum, and P. persicifolium constitutes a new approach to clarifying the taxonomic statuses. The numeric analysis of color, providing colorimetric variables, together with the detailed description of the metabolic profiles of populations with different flower colors, constitute a unique chemical fingerprint that identifies species and subspecies with clear markers. This study is the most complete metabolic research on genus Phyteuma, since we identified and quantified 44 phenolic compounds using HPLC-MS, comprising 14 phenolic acids, 23 flavonols and flavones, and, for the first time in the genus, 7 anthocyanins involved in flower color variability. This approach contributes to clarifying the differences between species, which is particularly relevant in taxonomic complexes such as the present, where morphology fails to clearly differentiate taxa at specific and intraspecific levels.

Olives ripen in the late autumn and represent a good source of nutrients that Halyomorpha halys uses to prepare for diapause. This is the first study to investigate the impact of H. halys infestation on the phenolic response and olive fruit quality in the pierced tissue of damaged fruits and in the non-pierced part of damaged fruits of ‘Istrska belica’ and ‘Pendolino’ cultivars. Both total phenolic content and antioxidant capacity contents significantly increased in the infested fruits of the cultivar ‘Istrska belica’. Total phenolic content in the pierced tissue of damaged fruits increased by 10.7%, while the content of AC in the non-pierced tissue of damaged fruits increased by 7.11% and in the pierced tissue of damaged fruits by 6.1% compared to control. A total of 44 individual phenolic compounds were identified, 21 of them increased in at least one cultivar after infestation. Huge increases in phenolic content were observed in both cultivars, particularly for flavones, secoiridoids, anthocyanins, and flavonols in the pierced tissue of damaged fruits. The most responsive individual phenolic compound in both cultivars was oleuropein. Its content in the pierced tissue of damaged fruits increased by 44.7% in the cultivar ‘Pendolino’ and for 82.6% in the cultivar ‘Istrska belica’.

Advances in molecular diagnostics have identified subsets of Ewing and Ewing-like sarcomas driven by variant translocations with unique biology. It is likely that patients with these tumours will have different clinical features and therapeutic outcomes. Nevertheless, the management of these patients both locally and within cooperative group trials depends on the local pathological diagnosis. It is not known what molecular diagnostic approaches are employed by local pathologists or if the exact translocation is commonly determined. In addition, it is not known what therapeutic approaches are employed for these patients or what cooperative trials are deemed appropriate for these patients by expert consensus. To answer these questions, we performed an international survey of oncologists and pathologists to better understand the diagnostic approaches used to identify variant translocations and the influence the findings have on therapy and clinical trial eligibility. An online survey was distributed to oncologists and pathologists primarily in North America. A total of 141 surveys were completed, representing a 28% response rate. The majority of respondents considered EWSR1-ETS gene family translocations (range 61–96%) to be Ewing sarcoma and would include them on the primary arm of a Ewing sarcoma clinical trial. There was a lack of consensus on how to classify and stratify BCOR-CCNB3, CIC-DUX4, and EWSR1+ with non-ETS partner fusions. Most respondents were either unsure how their institution tested, or their institution did not perform the test. In cases with atypical Ewing morphology, most respondents favoured additional fusion transcript testing. There is a lack of consensus regarding the classification and stratification of rare molecular subtypes in Ewing sarcoma. It is not clear how these alternative translocations have impacted outcomes for past clinical studies. This suggests a need for molecular confirmation of diagnoses and centralized or minimum standardization of testing for future trial enrolment.

The present study was carried out to investigate the yield, quality, and metabolomic responses of four different vegetable crops to treatments with pure juglone standard and walnut (Juglans regia L.) leaf extract at soil concentrations found in walnut orchards. A total of 60 phenolic compounds were identified and quantified, some for the first time in these crop vegetables. Beta vulgaris L. and Lactuca sativa L. were less susceptible to juglone. For crop quality, B. vulgaris showed the least effects of the different treatments. Both Brassica rapa L. var. japonica and Valerianella locusta Laterr. showed lower yields, even at the lower juglone concentration, and reduced quality, so their cultivation in juglone-containing soils should be avoided. This study also investigated leaf quality at different ages and the quality and yield of these crop vegetables grown under the influence of allelochemicals, to determine the influence of allelochemicals on metabolomics and, thus, on the uptake of phenolic compounds considered to be beneficial to human health.

Coffee and tea are popular beverages worldwide, and therefore generate large amounts of waste. Here we describe the caffeine content and phenolic profile in three types of teas and coffees, and how they vary with two successive extractions. Although the first extraction was far more efficient than the second, green tea also showed a high content of flavanols in the second extraction, as did mate tea for phenolic acids. Black tea could also be a good option since caffeine content was highest in both extractions. Water also proved to be the most effective solvent in almost all cases, which represent a major benefit for urban horticulture, as it is a simple extraction method from an easily accessible source. Coffee and tea residues are a rich source of caffeine and phenolic compounds that could potentially be used as alternatives to conventional pesticides.

Ewing sarcoma is a small round blue cell malignancy arising from bone or soft tissue and most commonly affects adolescents and young adults. Metastatic and relapsed Ewing sarcoma have poor outcomes and recurrences remain common. Owing to the poor outcomes associated with advanced disease and the need for a clear research strategy, the Children’s Oncology Group Bone Tumor Committee formed the New Agents for Ewing Sarcoma Task Force to bring together experts in the field to evaluate and prioritize new agents for incorporation into clinical trials. This group’s mission was to evaluate scientific and clinical challenges in moving new agents forward and to recommend agents and trial designs to the Bone Tumor Committee. The task force generated a framework for vetting prospective agents that included critical evaluation of each drug by using both clinical and non-clinical parameters. Representative appraisal of agents of highest priority, including eribulin, dinutuximab, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, anti-angiogenic tyrosine kinase inhibitors, and poly-ADP-ribose polymerase (PARP) inhibitors, is described. The task force continues to analyze new compounds by using the paradigm established.

Introducción y objetivos: La biología floral de Lantana camara, nativa del Centro y Sur de América e invasora cosmopolita, tiene aspectos desconocidos y controvertidos. El objetivo de este trabajo fue determinar el sistema reproductivo, atributos florales y polinizadores en una población ribereña del Río de la Plata. M&M: Se emplearon los métodos usuales de la biología de la polinización. El estudio se realizó en Ciudad Autónoma de Buenos Aires, Argentina, en la primavera de 2012. Resultados: Las flores emiten olor leve y dulce mediante osmóforos que rodean la entrada del tubo floral, coincidiendo con el patrón de absorción-reflexión en el espectro UV. El néctar se acumula en el tubo corolino, secretado probablemente por tricomas situados en la base. Durante la antesis, se suceden tres fases florales, distinguibles por cambios en la coloración de la corola, intensidad del aroma, cantidad de recompensa y madurez de las anteras y el estigma. Las flores, psicófilas, recibieron visitas de lepidópteros diurnos, y también de himenópteros, dípteros y colibríes. El mayor éxito reproductivo ocurrió con polinización libre; los índices de autocompatibilidad y P/O indicaron autocompatibilidad parcial y xenogamia facultativa, respectivamente. Conclusiones: L. camara se autopoliniza espontáneamente, probablemente una causa de su propagación global. Debido a su actividad en las flores, fase floral visitada, carga polínica y frecuencia de visitas sólo las mariposas Agraulis vanillae maculosa, Dryas iullia alcionea y Cymaenes sp. polinizarían en este sitio.

Ewing sarcoma cells depend on the EWS-FLI1 fusion transcription factor for cell survival. Using an assay of EWS-FLI1 activity and genome-wide RNAi screening, we have identified proteins required for the processing of the EWS-FLI1 pre-mRNA. We show that Ewing sarcoma cells harboring a genomic breakpoint that retains exon 8 of EWSR1 require the RNA-binding protein HNRNPH1 to express in-frame EWS-FLI1. We also demonstrate the sensitivity of EWS-FLI1 fusion transcripts to the loss of function of the U2 snRNP component, SF3B1. Disrupted splicing of the EWS-FLI1 transcript alters EWS-FLI1 protein expression and EWS-FLI1-driven expression. Our results show that the processing of the EWS-FLI1 fusion RNA is a potentially targetable vulnerability in Ewing sarcoma cells.

Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4). Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial.

ET-743 (trabectedin; Yondelis) is approved in Europe for the treatment of soft tissue sarcomas. Emerging phase 1 and 2 clinical data have shown high response rates in myxoid liposarcoma in part owing to the inhibition of the FUS-CHOP transcription factor. In this report, we show that modulation of specific oncogenic transcription factors by ET-743 may extend to other tumor types. We demonstrate that, among a panel of pediatric sarcomas, Ewing sarcoma family of tumors (ESFTs) cell lines bearing the EWS-FLI1 transcription factor are the most sensitive to treatment with ET-743 compared with osteosarcoma, rhabdomyosarcoma, and synovial sarcoma. We show that ET-743 reverses a gene signature of induced downstream targets of EWS-FLI1 in two different ESFT cell lines (P = .001). In addition, ET-743 directly suppresses the promoter activity of a known EWS-FLI1 downstream target NR0B1 luciferase reporter construct without changing the activity of a constitutively active control in ESFT cells. Furthermore, the effect is specific to EWS-FLI1, as forced expression of EWS-FLI1 in a cell type that normally lacks this fusion protein, HT1080 cells, induces the same NR0B1 promoter, but this activation is completely blocked by ET-743 treatment. Finally, we used gene set enrichment analysis to confirm that other mechanisms of ET-743 are active in ESFT cells. These results suggest a particular role for ET-743 in the treatment of translocation-positive tumors. In addition, the modulation of EWS-FLI1 makes it a novel targeting agent for ESFT and suggests that further development of this compound for the treatment of ESFT is warranted.