Project description:Several human cancers contain a small subpopulation of cells called cancer stem-like cells (CSCs)/cancer initiating cells (CICs), which are defined by the ability of self- renewal, multi-differentiation potential, and tumorigenesis. In current study, we focused on epithelioid sarcoma, which is very rare caner, and isolated CSCs/CICs from epitheloid sarcoma cell line ESX based on ALDH activity using ALDEFLUOR assay towards identification of a new CIC/CSC marker. We performed gene profiling between ALDHhigh and ALDH low cells using cDNA microarray for the identification of good markers of CSCs/CICs of epithelioid sarcoma.
Project description:Epithelioid Sarcoma (ES) is a rare neoplasm uniquely comprised of cells exhibiting both mesenchymal and epithelial features. Having propensity for local and distant recurrence, it can pose a diagnostic dilemma secondary to pathologic complexity. Patients have dismal prognosis due to lack of effective therapy. HDAC inhibitors exhibit marked anti-tumor effects in various malignancies. Our studies demonstrate that pan-HDAC inhibitors constitute potentially novel therapeutics versus ES. Human ES cells (VAESBJ, HS-ES, Epi544) were studied in vitro to evaluate the effects of HDACi. Gene array analysis was used to identify the impact of HDACi on ES gene expression in three cell lines.
Project description:Epithelioid Sarcoma (ES) is a rare neoplasm uniquely comprised of cells exhibiting both mesenchymal and epithelial features. Having propensity for local and distant recurrence, it can pose a diagnostic dilemma secondary to pathologic complexity. Patients have dismal prognosis due to lack of effective therapy. HDAC inhibitors exhibit marked anti-tumor effects in various malignancies. Our studies demonstrate that pan-HDAC inhibitors constitute potentially novel therapeutics versus ES. Human ES cells (VAESBJ, HS-ES, Epi544) were studied in vitro to evaluate the effects of HDACi.
Project description:Epithelioid hemangioendothelioma (EHE) is a rare vascular sarcoma that is associated with a WWTR1-CAMTA1 fusion gene in greater than 90% of cases. We aimed to investigate the transcriptional pathways activated in EHE. Total RNA was isolated from EHE tumors from surgical resection or autopsy specimens (n=6) followed by RNA-Seq. The results of this study identified a unique transcriptional profile for EHE and helped to validate a novel murine model of EHE.
Project description:Epithelioid hemangioendothelioma (EHE) is a rare vascular sarcoma that is associated with a WWTR1-CAMTA1 fusion gene in greater than 90% of cases. Cell lines were generated from WWTR1-CAMTA1 positive murine EHE tumors which also harbor a loss of CDKN2A. RNA sequencing was performed on cell lines.
Project description:Dysfunction of epigenetic modulators such as the SWI/SNF complex is involved in a wide spectrum of cancer entities, yet their precise role in carcinogenesis is not clear to date Among SWI/SNF-mutant entities, SMARCB1-deficient cancers such as Epithelioid Sarcoma (EpS) are characterized by this genetic event in an otherwise rather silent mutational landscape. However, its oncogenic role remains unclear. Here, we generate a panel of SMARCB1 re-expressing Epithelioid Sarcoma (EpS) cell lines and employ a functional multi-omics approach to characterize and compare the function of the residual SMARCB1-deficient and the physiological SWI/SNF complex in EpS. We show that SWI/SNF holds canonical characteristics of both tumor-suppressors and proto-oncogenes due to its multi-faceted role in the regulation of the epigenome. Our data indicates that the loss of SMARCB1 causes an overall loss of SWI/SNF chromatin affinity at cis-regulatory enhancer elements, inducing a preference for uncontrolled proliferation and cell cycle progression as opposed to development and differentiation. As epigenetic regulation is a dynamic complex, we further demonstrate that EpS cell lines depend on continuous residual SWI/SNF action to maintain clonogenicity and proliferation. Consequently, our models exhibit markedly increased sensitivity to pharmacological inhibition of the residual SWI/SNF when compared with SWI/SNF-proficient cancer entities. Collectively, our results shed new light on the pleiotropic, deregulated pathways upon SWI/SNF dysfunction in EpS and provide inroads for further therapeutic approaches.