Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor
| Autor: | Joseph A. Ludwig, Brian A. Menegaz, Suzanne Craig, Jalen A. Benson, Salah Eddine Lamhamedi-Cherradi, Xiao Ma, Gloria E. Garcia, Charles V. Kingsley, Cynthia R. Lockworth, Pamela Camacho, Andrea Hayes-Jordan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cancer Research Original article Desmoplastic small-round-cell tumor Tumor suppressor gene Pyridines medicine.medical_treatment Cell Apoptosis Desmoplastic Small Round Cell Tumor lcsh:RC254-282 Heterocyclic Compounds 4 or More Rings TRAIL TNF-related apoptosis inducing ligand 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor medicine Animals Humans Receptor WT1 Proteins Cell Proliferation Chemotherapy Cell growth business.industry Imidazoles Cancer Sarcoma DR4/DR5 Death Receptors medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Receptors TNF-Related Apoptosis-Inducing Ligand 030104 developmental biology medicine.anatomical_structure Pyrimidines 030220 oncology & carcinogenesis Cancer research DSRCT Desmoplastic Small Round Cell Tumor business |
| Zdroj: | Neoplasia (New York, N.Y.) Neoplasia: An International Journal for Oncology Research, Vol 20, Iss 5, Pp 524-532 (2018) |
| ISSN: | 1476-5586 |
| Popis: | Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT. |
| Databáze: | OpenAIRE |
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