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Specialty: Cancer & Oncology
Cancer: Ewing's Sarcoma

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Total 13 results found since Jan 2013.

Single-cell RNA profiling identifies diverse cellular responses to EWSR1/FLI1 downregulation in Ewing sarcoma cells
ConclusionsWe show that time-dependent changes induced by suppression of oncogenicEWSR1/FLI1 expression induces dormancy, with different subpopulation dynamics. Cells re-entering the proliferative cycle show enhanced stem-like characteristics, whereas those remaining dormant for prolonged periods appear to survive through autophagy. Cells with these characteristics identified in exponentially growing cell populations and in tumor xenografts may confer drug resistance and could potentially contribute to metastasis.
Source: Cellular Oncology - January 7, 2022 Category: Cancer & Oncology Source Type: research

Inhibition of CHK1 sensitizes Ewing sarcoma cells to the ribonucleotide reductase inhibitor gemcitabine.
In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR. However, clofarabine is a reversible inhibitor of RNR and we found that the effect of clofarabine is limited when using a short (6-hour) drug treatment. Gemcitabine, on the other hand, is an irreversible inhibitor of the RRM1 subunit of RNR and this drug induces apoptosis in Ewing sarcoma cells when used in both 6-hour and longer drug treatments. Treatment of Ewing sarcoma cells with gemcitabine also results in activation of checkpoint kinase 1 (CHK1), which is a crit...
Source: Oncotarget - November 22, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Identification of a Novel SYK/c-MYC/MALAT1 Signaling Pathway and Its Potential Therapeutic Value in Ewing Sarcoma.
CONCLUSIONS: The present study identifies a novel signaling involving SYK/c-MYC/MALAT1 as a promising therapeutic target for the treatment of EWS. PMID: 28336564 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - March 23, 2017 Category: Cancer & Oncology Authors: Sun H, Lin DC, Cao Q, Pang B, Gae DD, Lee VK, Lim HJ, Doan N, Said JW, Gery S, Chow M, Mayakonda A, Forscher C, Tyner JW, Koeffler HP Tags: Clin Cancer Res Source Type: research

Abstract A18: Epigenetic profiling uncovers the suppressive role of caveolae in Ewing sarcoma
Ewing sarcoma (ES) is the second most common bone tumor in childhood. ES harbors a characteristic gene translocation that gives rise to a fusion protein, most commonly EWS/FLI1 (EF). Caveolin-1 (CAV1) is a direct target of EF, it is overexpressed in ES and has an oncogenic role. CAV1 and the Polymerase I and transcript release factor (PTRF) interact at the plasma membrane and are essential for caveolae formation. The methylome analysis of ES samples and cell lines revealed a hypermethylation in the N-shore islands of the PTRF promoter compared to normal cells. We hypothesize that, as ES cells have very few caveolae and do ...
Source: Cancer Research - April 3, 2016 Category: Cancer & Oncology Authors: Huertas–Martinez, J., Court, F., Rello–Varona, S., Martin, D. H., Almacellas, O., Sainz–Jaspeado, M., Garcia–Monclus, S., Lagares–Tena, L., Buȷ, R., Hontecillas–Prieto, L., Mateo–Lozano, S., Sastre, A., Azo Tags: Epigenetics Source Type: research

Abstract A155: Small molecule metabolic inhibitors, compound A and the derivatives specifically inhibit the cell growth of Ewing's sarcoma cells harbor EWS-FLI1 in vitro and in vivo
Conclusions: Compound A and its derivatives may be a therapeutic agent with potent antitumor activity for Ewing's sarcoma patients.Citation Format: Hiromichi Kosaka, Yasuo Watanabe, Michihiro Maemoto, Masamori Sugawara, Miwa Watanabe, Yoko Ono, Yoshisuke Nakasato, Masahiro Matsubara, Ryuichiro Nakai. Small molecule metabolic inhibitors, compound A and the derivatives specifically inhibit the cell growth of Ewing's sarcoma cells harbor EWS-FLI1 in vitro and in vivo. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (P...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kosaka, H., Watanabe, Y., Maemoto, M., Sugawara, M., Watanabe, M., Ono, Y., Nakasato, Y., Matsubara, M., Nakai, R. Tags: Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts Source Type: research

Abstract 4966: Identification of deubiquitinating enzyme USP19 as a regulator of EWS/FLI1 protein turnover in Ewing sarcoma
Ewing sarcoma belongs to the family of pediatric tumors which arise most commonly in bone. The majority of Ewing sarcoma is characterized by a balanced translocation between chromosomes 11 and 22 which encodes for the uniquely expressed fusion protein EWS/FLI1. Tumor cells are crucially dependent on expression of the fusion protein. Protein degradation is an important and highly regulated process in all cells and novel insights are beginning to be applied for cancer therapy. We aim to investigate the mechanism of turnover with the goal to diminish EWS/FLI1 protein and thereby identify novel targets for Ewing sarcoma treatm...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Gierisch, M. E., Lopez-Garcia, L. A., Pfistner, F., Niggli, F. K., Schaefer, B. W. Tags: Molecular and Cellular Biology Source Type: research

Abstract 478: EWS/FLI1 transcription is modulated by the PI3K pathway via SP1 in Ewing sarcoma
Ewing sarcoma (ES) is the second most frequent bone cancer in childhood and it is characterized by the presence of the balanced t(11;22)(q24;q12) translocation in more than 85% of cases, generating a dysregulated transcription factor EWS/FLI1. ES belongs to small-round-blue-cell tumors and it is a very aggressive osteolytic cancer with early tendency for development of metastasis. Mostly it affects bones such as pelvis, femour and ribs but can also arise in soft tissues, mainly in adults. EWS/FLI1 is an essential oncogenic component of ES development which is necessary for tumor cell maintenance, through inappropriate regu...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Giorgi, C., Boro, A., Lopez-Garcia, L. A., Schaefer, B. W., Niggli, F. K. Tags: Tumor Biology Source Type: research

Abstract 479: Inhibition of the splicing of the EWS-FLI1 fusion transcript reverses EWS-FLI1 driven oncogenic expression in Ewing sarcoma
This study has implications for the treatment of ES through inhibition of proteins required for expression of the EWS-FLI1 transcript and identifies a candidate lead compound for further clinical development. Our findings may also open up strategies for treatment of other cancers driven by fusion oncogenes.Citation Format: Patrick J. Grohar, Suntae Kim, Sara Haddock, Guillermo Rangel Rivera, Matt Harlow, Nichole K. Maloney, Konrad Huppi, Kristen Gehlhaus, Magdalena Grandin, Carleen Klumpp-Thomas, Eugen Buehler, Lee J. Helman, Scott E. Martin, Natasha J. Caplen. Inhibition of the splicing of the EWS-FLI1 fusion transcript r...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Grohar, P. J., Kim, S., Haddock, S., Rangel Rivera, G., Harlow, M., Maloney, N. K., Huppi, K., Gehlhaus, K., Grandin, M., Klumpp-Thomas, C., Buehler, E., Helman, L. J., Martin, S. E., Caplen, N. J. Tags: Tumor Biology Source Type: research

Abstract A10: Functional characterization of Ewing's sarcoma susceptibility loci
Conclusions: In synopsis, our data indicate that the previously identified ES susceptibility regions and candidate genes may play a prominent role in ES pathobiology. Citation Format: Thomas Grunewald, Marie-Ming Aynaud, Franck Tirode, Eleni Tomazou, Didier Surdez, Thomas Rio Frio, Virginie Bernard, Virginie Raynal, Carlo Lucchesi, Gaelle Pierron, Pascale Gilardi-Hebenstreit, Patrick Charnay, Heinrich Kovar, Olivier Delattre. Functional characterization of Ewing's sarcoma susceptibility loci. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improve...
Source: Cancer Research - October 9, 2014 Category: Cancer & Oncology Authors: Grunewald, T., Aynaud, M.-M., Tirode, F., Tomazou, E., Surdez, D., Frio, T. R., Bernard, V., Raynal, V., Lucchesi, C., Pierron, G., Gilardi-Hebenstreit, P., Charnay, P., Kovar, H., Delattre, O. Tags: Genetic Predisposition to Pediatric Cancers Source Type: research

Abstract 3422: RNAi screening identifies FGFR4 as a modulator of growth and survival in Ewing sarcoma
Ewing sarcoma is the second most common cancer of bone and soft tissue arising in children and young adults. Standard treatment of Ewing sarcoma includes surgery, radiation, and chemotherapy largely consisting of combinations of non-targeted cytotoxic agents. Although the survival rate has improved for patients treated for localized disease, the survival rate of patients with metastatic tumor remains lower than 30%. In order to improve therapeutic options for Ewing Sarcoma, we employed a functional genomics approach based on RNA interference (RNAi) screening to identify genes whose silencing affected the proliferation and ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Azorsa, D. O., Gonzales, I. M., Arora, S., Hagelstrom, R. T., Little, T. H., Arceci, R. J., Mousses, S. Tags: Molecular and Cellular Biology Source Type: research

Abstract 3989: High throughput screening highlights NFkB signaling in Ewing sarcoma
Ewing sarcoma (ES) is the second most frequent pediatric bone tumor and still remains of poor prognosis especially for metastatic patients. Genetically, ES is characterized by a chromosomal translocation between EWSR1 and ETS family members (FLI1 in 85% of cases). This leads to the expression of EWS-FLI1 chimeric oncogene transcription factor. Aiming at identifying EWS-FLI1 regulated genes with potential therapeutic targets, a genome wide method was developed to rank these potential hits by combining Ewing sarcoma transcriptome and ChIPSeq data. Accordingly, 273 selected genes were further investigated using a siRNA approa...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Surdez, D., Stoll, G., Tirode, F., Laud, K., Barillot, E., Delattre, O. Tags: Tumor Biology Source Type: research

Dual targeting of EWS-FLI1 activity and the associated DNA damage response with Trabectedin and SN38 synergistically inhibits Ewing sarcoma cell growth.
CONCLUSIONS: These results provide the basis and rationale for translating this drug combination to the clinic. In addition, the study highlights an approach that utilizes a targeted agent to interfere with an oncogenic transcription factor and then exploits the resulting changes in gene expression to develop a molecularly targeted combination therapy. PMID: 24277455 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - November 25, 2013 Category: Cancer & Oncology Authors: Grohar PJ, Segars LE, Yeung C, Pommier Y, D'Incalci M, Mendoza A, Helman LJ Tags: Clin Cancer Res Source Type: research