A5020727795- Neurofibromatosis and Schwannoma Cases
- Sarcoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Immune cells in cancer
- Immune Cell Function and Interaction
- Melanoma and MAPK Pathways
- T-cell and B-cell Immunology
- Bone Tumor Diagnosis and Treatments
- Neuroendocrine Tumor Research Advances
- Cancer Cells and Metastasis
- Glioma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Chemokine receptors and signaling
University of Minnesota Medical Center
2020-2023
University of Minnesota
2019-2023
Abstract Background Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1). To address the critical need for novel therapeutics MPNST, we aimed to establish an ex vivo 3D platform accurately captured genomic diversity of MPNST and could be utilized a medium-throughput manner drug screening studies validated using patient-derived xenografts (PDX). Methods Genomic analysis was performed on all...
CD8αα intraepithelial lymphocytes (IELs) are abundant T cells that protect the gut epithelium. Their thymic precursors (IELps) include PD-1+ type A and Tbet+ B populations, which differ in their antigen-receptor specificities. To better understand IEL ontogeny, we performed “time-stamp” fate mapping experiments observed it seeds intestine predominantly during a narrow time window early life. Adoptively transferred IELps parked intestines of young mice than adults. In mice, both had an S1PR1+...
Abstract Background The MEK1/2 inhibitor selumetinib was recently approved for neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas, but outcomes could be improved and its pharmacodynamic evaluation in other relevant tissues is limited. aim of this study to assess tissue pharmacokinetics (PK) pharmacodynamics (PD) using a minipig model NF1. Methods WT (n = 8) NF1 minipigs received single oral dose 7.3 mg/kg selumetinib. Peripheral blood mononuclear cells (PBMCs), cerebral...
Abstract Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1-MPNST), but can occur sporadically. Through a multi-institution collaboration, we have developed 13 NF1-associated MPNST patient-derived xenografts (PDX). Genomic analysis of the PDX-tumor pairs identified somatic mutations NF1 (61%), SUZ12 EED (15%), and TP53 chromosome 8 (Chr8) gain (77%), consistent published data. Pre-clinical...
Abstract We have employed gene-editing technology to create a Neurofibromatosis Type 1 (NF1) minipig that replicates the broad spectrum of disease develops in NF1 patients and meets National Institute Health’s diagnostic criteria for NF1. The boars are fertile mutant allele is transmitted at Mendelian rate with no reduction fitness offspring inherit this allele. To date, we observed 100% penetrance café au lait macules, phenotype occurs nearly every patient, but has never been demonstrated...
Abstract Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in the neurofibromin gene. NF1 patients present with variety of clinical manifestations and are predisposed to cancer development. Many animal models have been developed, yet none display spectrum seen translational impact these has limited. Using gene-editing technology, we developed minipig model that exhibits hallmarks disease, including café au lait macules, neurofibromas, optic pathway glioma. We conducted...