scholarly journals The dual inhibitory effect of thiostrepton on FoxM1 and EWS/FLI1 provides a novel therapeutic option for Ewing’s sarcoma

2013 ◽  
Vol 43 (3) ◽  
pp. 803-812 ◽  
Author(s):  
ANIRUDDHA SENGUPTA ◽  
MAHBUBUR RAHMAN ◽  
SILVIA MATEO-LOZANO ◽  
OSCAR M. TIRADO ◽  
VICENTE NOTARIO
Keyword(s):  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Therapeutic Option ◽  
Inhibitory Effect ◽  
Novel Therapeutic

Abstract 3408: RNAi screening identifies STK10 as a novel therapeutic target for Ewing's sarcoma

2010 ◽  
Author(s):  
Shilpi Arora ◽  
Irma M. Gonzales ◽  
Chao Sima ◽  
Javed Khan ◽  
Spyro Mousses ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Rnai Screening ◽  
Novel Therapeutic

scholarly journals An Innovative Therapeutic Option for the Treatment of Skeletal Sarcomas: Elimination of Osteo- and Ewing’s Sarcoma Cells Using Physical Gas Plasma

2020 ◽  
Vol 21 (12) ◽  
pp. 4460 ◽  
Author(s):  
Josephine M. Jacoby ◽  
Silas Strakeljahn ◽  
Andreas Nitsch ◽  
Sander Bekeschus ◽  
Peter Hinz ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Therapeutic Option ◽  
Bone Sarcoma ◽  
Atmospheric Plasma ◽  
Local Surgery ◽  
Release Assay ◽  
Sarcoma Cells

Osteosarcoma and Ewing’s sarcoma are the most common malignant bone tumors. Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve the clinical outcome for patients. However, they are accompanied by acute and chronic side effects that affect the quality of life of patients, motivating novel research lines on therapeutic options for the treatment of sarcomas. Previous experimental work with physical plasma operated at body temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on different cancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcoma entities, osteosarcoma and Ewing’s sarcoma, which were represented by four cell lines (U2-OS, MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lines was observed. CAP-induced alterations in cell membrane functionality were detected by performing a fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications of the cell membrane and modifications in the actin cytoskeleton composition were examined using fluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore, the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays. The observations suggest that a single CAP treatment of bone sarcoma cells may have significant anti-oncogenic effects and thus may be a promising extension to existing applications.

Abstract 2961: Reactivation of EWS-FLI1 suppressed FOXO1 expression as a novel therapeutic strategy for Ewing's sarcoma

2012 ◽  
Author(s):  
Stephan Niedan ◽  
Max Kauer ◽  
Gunhild Jug ◽  
Robert L. Walker ◽  
Paul S. Meltzer ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Novel Therapeutic

scholarly journals Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
David Herrero-Martin ◽  
Argyro Fourtouna ◽  
Stephan Niedan ◽  
Lucia T. Riedmann ◽  
Raphaela Schwentner ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Therapeutic Agents ◽  
Chromosomal Translocations ◽  
Chimeric Proteins ◽  
Fatal Disease ◽  
Factors Affecting ◽  
Factors Influencing ◽  
Novel Therapeutic

Ewing's sarcoma family tumors (ESFT) are characterized by specific chromosomal translocations, which give rise to EWS-ETS chimeric proteins. These aberrant transcription factors are the main pathogenic drivers of ESFT. Elucidation of the factors influencing EWS-ETS expression and/or activity will guide the development of novel therapeutic agents against this fatal disease.

scholarly journals Primary renal Ewing’s sarcoma in an adult: an enigma

2021 ◽  
Vol 5 (3-4) ◽  
pp. 111-113
Author(s):  
Suvraraj Das ◽  
Gaurav Aggarwal ◽  
Sujoy Gupta ◽  
Divya Midha
Keyword(s):  
Renal Vein ◽  
Radical Nephrectomy ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Imaging Modality ◽  
Therapeutic Option ◽  
Left Renal Vein ◽  
In Situ Hybridisation ◽  
Imaging Features ◽  
Ultrasound Evaluation

AbstractObjectivesExtraskeletal Ewing’s sarcoma is a rarity, with a renal primary in an adult, being even rarer. There is no consensus on the optimal imaging modality, as well as best therapeutic option, making them an enigma for clinicians.Case presentationWe report the case of a 34-year-old lady, a known case of invasive lobular carcinoma of the left breast (ER,PR positive, Her2neu negative), having completed treatment in 2017, wherein, on an ultrasound evaluation for left flank pain, was incidentally found to have a left renal mass. A CT scan corroborated with the ultrasound, with an additional Level 1, left renal vein thrombus. She underwent an open left radical nephrectomy with renal vein thrombectomy. Histopathology of the resected tumor revealed features of Ewing’s sarcoma of the kidney, confirmed by Fluorescent In Situ Hybridisation (FISH) and Immunohistochemistry (IHC).ConclusionPrimary renal Ewing’s sarcoma in an adult is a rare occurrence, with no characteristic imaging features, and no universally accepted guideline based management protocols. Akin with standard Ewings sarcoma treatment strategies, a margin negative- radical nephrectomy with adjuvant chemotherapy, seems the most apt treatment strategy.

scholarly journals Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy

2011 ◽  
Vol 34 (3) ◽  
pp. 131-145 ◽  
Author(s):  
Michela Pasello ◽  
Maria Cristina Manara ◽  
Francesca Michelacci ◽  
Marilù Fanelli ◽  
Claudia Maria Hattinger ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Therapeutic Option ◽  
In Vivo Studies ◽  
Whole Body ◽  
Drug Resistant ◽  
Glutathione S Transferase ◽  
Positive Interaction

Recent studies have indicated that targeting glutathione-S-transferase (GST) isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST). NBDHEX showed a relevantin vitroactivity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. Thein vitroactivity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.

scholarly journals Exploiting Gangliosides for the Therapy of Ewing’s Sarcoma and H3K27M-Mutant Diffuse Midline Glioma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 520
Author(s):  
Arthur Wingerter ◽  
Khalifa El Malki ◽  
Roger Sandhoff ◽  
Larissa Seidmann ◽  
Daniel-Christoph Wagner ◽  
...  
Keyword(s):  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Therapeutic Option ◽  
Intracranial Metastasis ◽  
Pediatric Tumor ◽  
Ganglioside Metabolism ◽  
Intermediate Expression ◽  
Diffuse Midline Glioma ◽  
Tumor Entities

The ganglioside GD2 is an important target in childhood cancer. Nevertheless, the only therapy targeting GD2 that is approved to date is the monoclonal antibody dinutuximab, which is used in the therapy of neuroblastoma. The relevance of GD2 as a target in other tumor entities remains to be elucidated. Here, we analyzed the expression of GD2 in different pediatric tumor entities by flow cytometry and tested two approaches for targeting GD2. H3K27M-mutant diffuse midline glioma (H3K27M-mutant DMG) samples showed the highest expression of GD2 with all cells strongly positive for the antigen. Ewing’s sarcoma (ES) samples also showed high expression, but displayed intra- and intertumor heterogeneity. Osteosarcoma had low to intermediate expression with a high percentage of GD2-negative cells. Dinutuximab beta in combination with irinotecan and temozolomide was used to treat a five-year-old girl with refractory ES. Disease control lasted over 12 months until a single partially GD2-negative intracranial metastasis was detected. In order to target GD2 in H3K27M-mutant DMG, we blocked ganglioside synthesis via eliglustat, since dinutuximab cannot cross the blood–brain barrier. Eliglustat is an inhibitor of glucosylceramide synthase, and it is used for treating children with Gaucher’s disease. Eliglustat completely inhibited the proliferation of primary H3K27M-mutant DMG cells in vitro. In summary, our data provide evidence that dinutuximab might be effective in tumors with high GD2 expression. Moreover, disrupting the ganglioside metabolism in H3K27M-mutant DMG could open up a new therapeutic option for this highly fatal cancer.

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