A5054130715- Sarcoma Diagnosis and Treatment
- Hippo pathway signaling and YAP/TAZ
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- RNA modifications and cancer
- Eosinophilic Disorders and Syndromes
- Fibroblast Growth Factor Research
- Tumors and Oncological Cases
- RNA Research and Splicing
- Radiomics and Machine Learning in Medical Imaging
- CAR-T cell therapy research
- Kruppel-like factors research
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Renal and related cancers
- FOXO transcription factor regulation
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Plant Disease Resistance and Genetics
- Circular RNAs in diseases
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
Duke University
2016-2025
Duke Medical Center
2014-2025
Duke University Hospital
2011-2025
University of Toronto
2023
University Health Network
2023
Princess Margaret Cancer Centre
2023
Duke University Health System
2020
National Cancer Institute
2017
Center for Cancer Research
2017
Centre for Cancer Biology
2007
Sphingomyelin hydrolysis and ceramide generation have been implicated in a signal transduction pathway that mediates the effects of tumor necrosis factor-α (TNF-α) other agents on cell growth differentiation. In many leukemic cells, TNF-α causes DNA fragmentation, which leads to programmed death (apoptosis). C 2 -ceramide (0.6 5 μM), synthetic cell-permeable analog, induced internucleosomal was inhibited by zinc ion. Other amphiphilic lipids failed induce apoptosis. The closely related...
PURPOSE Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond PAX-FOXO1 fusion status, no genomic markers are available risk stratification. We present an international consortium study designed to determine incidence driver mutations their association clinical outcome. PATIENTS AND METHODS Tumor samples collected from enrolled on Children's Oncology...
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence. Despite intergroup clinical trials conducted in Europe North America, outcomes for high risk patients with this disease have not significantly improved last several decades, survival metastatic or relapsed remains extremely poor. Accrual into new slow difficult, so vitro cell-line research vivo xenograft models present an attractive alternative preclinical cancer type. Currently, 30 commonly used...
Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression the paired box 3-forkhead protein O1 (PAX3-FOXO1) fusion oncogene. Despite its discovery nearly two decades ago, mechanisms which PAX3-FOXO1 drives tumor development are not well characterized. Previously, we reported that supports aRMS initiation enabling bypass cellular senescence checkpoints. We have now found this occurs in part through PAX3-FOXO1-mediated upregulation RASSF4, a...
Abstract Purpose: Rhabdomyosarcoma (RMS) is a malignancy with features of skeletal muscle, and the most common soft tissue sarcoma childhood. Survival for high-risk groups approximately 30% at 5 years there are no durable therapies tailored to its genetic aberrations. During modeling RMS variants, embryonal (eRMS) alveolar (aRMS), we noted that receptor tyrosine kinase (RTK) fibroblast growth factor 4 (FGFR4) was upregulated as an early event in aRMS. Herein, evaluated expression FGFR4 eRMS...
Tumor-propagating cells (TPCs) share self-renewal properties with normal stem and drive continued tumor growth. However, mechanisms regulating TPC are largely unknown, especially in embryonal rhabdomyosarcoma (ERMS)-a common pediatric cancer of muscle. Here, we used a zebrafish transgenic model ERMS to identify role for intracellular NOTCH1 (ICN1) increasing TPCs by 23-fold. ICN1 expanded enabling the de-differentiation into self-renewing myf5+ TPCs, breaking rigid differentiation...
Importance Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma. Objective To assess whether CPVs are associated outcome among Design, Setting, Participants In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed rhabdomyosarcoma who treated across 171 Children’s Oncology Group sites from March 15, 1999, December 8, 2017. Data analysis...
Although great progress has been made at identifying and characterizing individual genes involved in cancer, less is known about how the combination of such collaborate to form tumors humans. To this end, we sought genetically recreate tumorigenesis normal human cells using altered cancer. We now show that expression mammalian proteins inactivate tumor suppressors Rb p53 conjunction with oncoproteins Ras Myc telomerase subunit hTERT sufficient drive a number somatic tumorigenic fate. This...
Ceramide has been suggested as an intracellular modulator of cell growth and differentiation [Okazaki, T. et al. (1990) J. Biol. Chem. 265, 15823-15831]. In this study, parameters that modulate the effects ceramide on HL-60 were examined. A short-chain, cell-permeable analog ceramide, C2-ceramide, induced human leukemia cells inhibited in a concentration-dependent manner. The potency C2-ceramide was modulated by starting density such concentration producing 50% inhibition (IC50%) ranged from...
Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with a histologic variant RMS known as alveolar (aRMS) have 5-year survival rate <30%. aRMS tissues exhibit number genetic changes, including loss-of-function p53 Rb tumor suppressor pathways, amplification MYCN, stabilization telomeres, characteristically, reciprocal translocation loci involving PAX FKHR genes, generating PAX7-FKHR or PAX3-FKHR...
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, whereas undifferentiated pleomorphic (UPS) one of sarcomas diagnosed adults. To investigate myogenic cell(s) origin these sarcomas, we used Pax7-CreER and MyoD-CreER mice to transform Pax7(+) MyoD(+) progenitors by expressing oncogenic Kras(G12D) deleting Trp53 vivo. developed RMS UPS, UPS. Using gene set enrichment analysis, UPS each clustered specifically within their human counterparts. These results suggest that...
Rhabdomyosarcoma (RMS), a cancer characterized by skeletal muscle features, is the most common soft-tissue sarcoma of childhood. While low- and intermediate-risk groups have seen improved outcomes, high-risk patients still face 5-year survival rate <30%, statistic that has not changed in over 40 years. Understanding biologic underpinnings RMS critical. The developmental pathways Notch YAP been identified as potent but independent oncogenic signals support embryonal variant (eRMS). Here,...
The two major types of rhabdomyosarcoma (RMS) are predominantly diagnosed in children, namely embryonal (ERMS) and alveolar (ARMS) RMS, patients treated with cytotoxic drugs, which results multiple toxic side effects later life. Therefore, development innovative chemotherapeutic strategies is imperative, a recent genomic analysis suggested the potential efficacy reactive oxygen species (ROS)-inducing agents. Here, we demonstrate potent histone deacetylase (HDAC) inhibitors, panobinostat...
Abstract Rhabdomyosarcoma, a malignancy showing features of skeletal muscle differentiation, is the most common soft tissue sarcoma childhood. The identification distinct clinical presentation patterns, histologic tumor types, and risk groups suggests that rhabdomyosarcoma collection highly related sarcomas rather than single entity. In an effort to understand this seemingly heterogeneous malignancy, we constructed genetically defined but malleable model by converting less differentiated...