scholarly journals The combination of epigenetic drugs SAHA and HCI-2509 synergistically inhibits EWS-FLI1 and tumor growth in Ewing sarcoma

Oncotarget ◽  
2018 ◽  
Vol 9 (59) ◽  
pp. 31397-31410 ◽  
Author(s):  
Daniel Jose García-Domínguez ◽  
Lourdes Hontecillas-Prieto ◽  
Pablo Rodríguez-Núñez ◽  
Guillem Pascual-Pasto ◽  
Monica Vila-Ubach ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Ewing Sarcoma ◽  
Epigenetic Drugs

scholarly journals Chemokine Expression Is Involved in the Vascular Neogenesis of Ewing Sarcoma: A Preliminary Analysis of the Early Stages of Angiogenesis in a Xenograft Model

2018 ◽  
Vol 22 (1) ◽  
pp. 30-39
Author(s):  
Francisco Giner ◽  
José A López-Guerrero ◽  
Antonio Fernández-Serra ◽  
Isidro Machado ◽  
Empar Mayordomo-Aranda ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Nude Mice ◽  
Ewing Sarcoma ◽  
Xenograft Model ◽  
Bone Cancer ◽  
Mouse Serum ◽  
Early Stages ◽  
Peritumoral Stroma ◽  
Ligand Expression

Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). Methods The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm–4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymic Balb-c nude mice (n = 14 each). The animals were sacrificed at 24, 48, and 96 hours and at 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularization experiments). Results We observed histological, ultrastructural, and immunohistochemical changes in the xenografted tumor at different times after implantation. Chemokine ligand expression peaked twice, once during the first 48 hours and again in the second week. We observed that tumor cells in contact with murine peritumoral stroma presented higher expression of chemokine ligands as well as more tumor cells around the capillary vessels. Mouse serum vascular endothelial growth factor levels peaked twice, once in the first hours and then in the second week after tumor implantation. Conclusion Chemokines and other angiogenic factors may be relevant in the angiogenic mechanism during tumor growth. This model provides information on the early stages of the angiogenic process and could be a useful tool in researching anti-angiogenic drugs for new therapeutic strategies in EWS.

scholarly journals Targeted inhibition of histone deacetylase leads to suppression of Ewing sarcoma tumor growth through an unappreciated EWS-FLI1/HDAC3/HSP90 signaling axis

2019 ◽  
Vol 97 (7) ◽  
pp. 957-972 ◽  
Author(s):  
Yan Ma ◽  
Michael Baltezor ◽  
Lian Rajewski ◽  
Jennifer Crow ◽  
Glenson Samuel ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Histone Deacetylase ◽  
Ewing Sarcoma ◽  
Signaling Axis ◽  
Targeted Inhibition

scholarly journals Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma

2019 ◽  
Vol 79 (19) ◽  
pp. 5060-5073 ◽  
Author(s):  
Choh Yeung ◽  
Anna E. Gibson ◽  
Sameer H. Issaq ◽  
Nobu Oshima ◽  
Joshua T. Baumgart ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Tumor Growth ◽  
Ewing Sarcoma ◽  
Preclinical Models

Evaluation of the multi-kinase inhibitor regorafenib in the Pediatric Preclinical Testing Consortium osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma in vivo models.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10038-10038
Author(s):  
Douglas James Harrison ◽  
Jonathan Benjamin Gill ◽  
Michael Roth ◽  
Wendong Zhang ◽  
Beverly Teicher ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Ewing Sarcoma ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Primary Treatment ◽  
Tumor Growth Inhibition ◽  
Oral Gavage ◽  
Preclinical Testing ◽  
In Vivo Models

10038 Background: Regorafenib is a multi-kinase inhibitor, developed by adding a fluorine atom to the phenyl ring of sorafenib. Regorafenib inhibits multiple kinases including BRAF, FGFR1, KIT, PDGFRB, RAF, RET, and VEGFR1-3, many at a higher potency than sorafenib. Prior studies within the Pediatric Preclinical Testing Consortium (PPTC) demonstrated sorafenib exhibited intermediate activity for tumor growth inhibition in more than 50% of the sarcoma models tested at a dose of 60mg/kg by oral gavage daily (5 days/wk for 6 consecutive weeks). The in vivo effects of regorafenib were studied in the PPTC osteosarcoma (OS), rhabdomyosarcoma (Rh) and Ewing (EW) sarcoma xenograft models. Methods: The in vivo anticancer effects of regorafenib were assessed in a panel of 6 osteosarcoma models (OS2, OS9, OS31, OS33, OS36, OS60), two rhabdomyosarcoma models (Rh30, Rh41), and one Ewing sarcoma model (EW5). Regorafenib was administered by oral gavage at a dose of 30 mg/kg/day given daily for 21 consecutive days. Time to event and tumor volume responses were defined and analyzed utilizing standard PPTC statistical methods. Results: Regorafenib induced significant improvements in event-free survival (EFS) compared to control in 100% (9/9) of sarcoma models tested. Most models showed pronounced slowing of tumor growth compared to control during the 21 days of regorafenib treatment, with tumor growth generally approximating control rates soon after completion of regorafenib treatment. Three out of 8 sarcoma models demonstrated EFS T/C values > 2 (1/6 OS, 2/2 Rh, 0/1 EW). Minimum relative tumor volumes ranged from 0.74 to 1.60, with no models meeting criteria for objective response. Conclusions: Regorafenib induced modest inhibition of tumor growth in the PPTC sarcoma models evaluated. The overall pattern of response to the multi-kinase inhibitor regorafenib against the PPTC sarcoma models appears similar to that of the kinase inhibitor sorafenib, with pronounced slowing of tumor growth in some models that is limited to the period of agent administration being the primary treatment effect.

TNF-Related Apoptosis Inducing Ligand (TRAIL) inhibits primary bone tumor growth and augments survival in a human model ewing sarcoma

Bone ◽  
2008 ◽  
Vol 42 ◽  
pp. S94
Author(s):  
Loic Geffroy ◽  
Damien Chauviere ◽  
Francois Lamoureux ◽  
Gaelle Picarda ◽  
Olivier Delattre ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Bone Tumor ◽  
Ewing Sarcoma ◽  
Human Model ◽  
Primary Bone Tumor ◽  
Primary Bone

scholarly journals The CXCR4-CXCL12 axis in Ewing sarcoma: promotion of tumor growth rather than metastatic disease

2012 ◽  
Vol 2 (1) ◽  
pp. 24 ◽  
Author(s):  
Dagmar Berghuis ◽  
Marco W Schilham ◽  
Susy J Santos ◽  
Suvi Savola ◽  
Helen J Knowles ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Metastatic Disease ◽  
Ewing Sarcoma

scholarly journals Neuronal Repressor REST Controls Ewing Sarcoma Growth and Metastasis by Affecting Vascular Pericyte Coverage and Vessel Perfusion

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1405
Author(s):  
Zhichao Zhou ◽  
Yuanzheng Yang ◽  
Fei Wang ◽  
Eugenie S. Kleinerman
Keyword(s):  
Tumor Growth ◽  
Ewing Sarcoma ◽  
Vascular Function ◽  
Fusion Gene ◽  
Critical Role ◽  
Survival Rates ◽  
Tumor Vasculature ◽  
Tumor Growth And Metastasis

Survival rates for Ewing sarcoma (ES) patients with metastatic disease have not improved in over 20 years. Tumor growth and metastasis are dependent on tumor vasculature expansion; therefore, identifying the regulators that control this process in ES may provide new therapeutic opportunities. ES expresses high levels of repressor element 1 silencing transcription factor (REST), which is regulated by the EWS-FLI-1 fusion gene. However, the role of REST in ES growth and the regulation of the tumor vasculature have not been elucidated. To study this role, we established REST-knockout human TC71 ES cell lines through CRISPR/Cas9 recombination. While knockout of REST did not alter tumor cell proliferation in vitro, REST knockout reduced tumor growth and metastasis to the lung in vivo and altered tumor vascular morphology and function. Tumor vessels in the REST-knockout tumors had a punctate appearance with significantly decreased tumor vascular pericytes, decreased perfusion, and increased permeability. REST-knockout tumors also showed increased apoptosis and hypoxia. These results indicate that REST plays a critical role in ES vascular function, which in turn impacts the ability of ES tumors to grow and metastasize. These findings therefore provide a basis for the targeting of REST as a novel therapeutic approach in ES.

Abstract 5714: Targeting serine metabolism impairs tumor growth in preclinical models of Ewing sarcoma

2020 ◽  
Author(s):  
Sameer Issaq ◽  
Arnulfo Mendoza ◽  
Tracy Rosales ◽  
Christine Heske ◽  
Craig Thomas ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Ewing Sarcoma ◽  
Preclinical Models ◽  
Serine Metabolism

scholarly journals Reversible LSD1 Inhibition Interferes with Global EWS/ETS Transcriptional Activity and Impedes Ewing Sarcoma Tumor Growth

2014 ◽  
Vol 20 (17) ◽  
pp. 4584-4597 ◽  
Author(s):  
Savita Sankar ◽  
Emily R. Theisen ◽  
Jared Bearss ◽  
Timothy Mulvihill ◽  
Laura M. Hoffman ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Ewing Sarcoma ◽  
Transcriptional Activity
Sign in / Sign up

Export Citation Format

Share Document