Medical Specialties Commons^™

Inducing Mitotic Catastrophe As A Therapeutic Approach To Improve Outcomes In Ewing Sarcoma., Soumya M. Turaga, Vikalp Vishwakarma, Stacey L. Hembruff, Benjamin K. Gibbs, Priya Sabu, Rajni V. Puri, Harsh B. Pathak, Glenson Samuel, Andrew K. Godwin

Manuscripts, Articles, Book Chapters and Other Papers

Ewing sarcoma (EWS) is an aggressive pediatric malignancy of the bone and soft tissues in need of novel therapeutic options. To identify potential therapeutic targets, we focused on essential biological pathways that are upregulated by EWS-FLI1, the primary oncogenic driver of EWS, including mitotic proteins such as Aurora kinase A (AURKA) and kinesin family member 15 (KIF15) and its binding partner, targeting protein for Xklp2 (TPX2). KIF15/TPX2 cooperates with KIF11, a key mitotic kinesin essential for mitotic spindle orientation. Given the lack of clinical-grade KIF15/TPX2 inhibitors, we chose to target KIF11 (using SB-743921) in combination with AURKA (using VIC-1911) given …

Identification Of Small Extracellular Vesicle Protein Biomarkers For Pediatric Ewing Sarcoma., Soumya M. Turaga, Mihaela E. Sardiu, Vikalp Vishwakarma, Amrita Mitra, Leonidas E. Bantis, Rashna Madan, Michael L. Merchant, Jon B. Klein, Glenson Samuel, Andrew K. Godwin

Manuscripts, Articles, Book Chapters and Other Papers

Ewing Sarcoma (EWS) is the second most common osseous malignancy in children and young adults after osteosarcoma, while it is the fifth common osseous malignancy within adult age population. The clinical presentation of EWS is quite often non-specific, with the most common symptoms at presentation consisting of pain, swelling or general discomfort. The dearth of clinically relevant diagnostic or predictive biomarkers continues to remain a pressing clinical challenge. Identification of tumor specific biomarkers can lend towards an early diagnosis, expedited initiation of therapy, monitoring of therapeutic response, and early detection of recurrence of disease. We carried-out a complex analysis of …

Perinucleolar Compartment (Pnc) Prevalence As An Independent Prognostic Factor In Pediatric Ewing Sarcoma: A Multi-Institutional Study., Elizabeth Gonzalez, Atif A. Ahmed, Laura Mccarthy, Katherine Chastain, Sahibu Sultan M Habeebu, Marta Zapata-Tarres, Rocio Cardenas-Cardos, Liliana Velasco-Hidalgo, Celso Corcuera-Delgado, Rodolfo Rodriguez-Jurado, Lilia García-Rodríguez, Alejandro Parrales, Tomoo Iwakuma, Midhat S. Farooqi, Brian R. Lee, Scott J. Weir, Terrie Flatt

Manuscripts, Articles, Book Chapters and Other Papers

The perinucleolar compartment (PNC) is a small nuclear body that plays important role in tumorigenesis. PNC prevalence correlates with poor prognosis and cancer metastasis. Its expression in pediatric Ewing sarcoma (EWS) has not previously been documented. In this study, we analyzed 40 EWS tumor cases from Caucasian and Hispanic patients for PNC prevalence by immunohistochemical detection of polypyrimidine tract binding protein and correlated the prevalence with dysregulated microRNA profiles. EWS cases showed staining ranging from 0 to 100%, which were categorized as diffuse (≥77%, n = 9, high PNC) or not diffuse (p= 0.017) and in patients who relapsed with …

Ewing Sarcoma Family Of Tumors-Derived Small Extracellular Vesicle Proteomics Identify Potential Clinical Biomarkers., Glenson Samuel, Jennifer Crow, Jon B. Klein, Michael L. Merchant, Emily Nissen, Devin C. Koestler, Kris Laurence, Xiaobo Liang, Kathleen Neville, Vincent S. Staggs, Atif Ahmed, Safinur Atay, Andrew K. Godwin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Ewing Sarcoma Family of Tumors (ESFT), the second most common pediatric osseous malignancy, are characterized by the pathognomonic chromosomal EWS-ETS translocation. Outside of tumor biopsy, no clinically relevant ESFT biomarkers exist. Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging. To identify new, clinically relevant biomarkers we evaluated the proteome of a subset of ESFT-derived small extracellular vesicles (sEVs).

Materials and methods: We performed the first high quality proteomic study of ESFT-derived sEVs from 5 ESFT cell lines representing the most common EWS-ETS fusion types and …