A5021400858- Neurofibromatosis and Schwannoma Cases
- Neuroblastoma Research and Treatments
- Nerve injury and regeneration
- Sarcoma Diagnosis and Treatment
- Meningioma and schwannoma management
- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Glioma Diagnosis and Treatment
- Soft tissue tumors and treatment
- Genetics and Neurodevelopmental Disorders
- Signaling Pathways in Disease
- Melanoma and MAPK Pathways
- Vascular Malformations Diagnosis and Treatment
- Cancer Research and Treatments
- Multiple Myeloma Research and Treatments
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
2019-2024
Institute of Predictive and Personalized Medicine of Cancer
2020
Centro de Investigación Biomédica en Red de Cáncer
2019
Plexiform neurofibromas (pNFs) are developmental tumors that appear in neurofibromatosis type 1 individuals, constituting a major source of morbidity and potentially transforming into highly metastatic sarcoma (MPNST). pNFs arise after NF1 inactivation cell the neural crest (NC)-Schwann (SC) lineage. Here, we develop an iPSC-based NC-SC vitro differentiation system construct lineage expression roadmap for analysis different 2D 3D NF models. The best model consists generating heterotypic...
<p>Combination indexes and curves for selected combinations all 9 MPNST cell lines</p>
<p>Photographs of each individual tumor after the different co-treatments in vivo</p>
<p>Analyses of the molecular targets triple treatment in vivo SP-10 MPNST PDOX</p>
<p>Evaluation of three down or up regulated genes after BETi treatment in MPNST cell lines</p>
<p>Dose response curves for all 28 single inhibitors in three independent MPNST cell lines</p>
<p>Photographs of each individual tumor after the triple treatment in vivo</p>
<p>Analysis of macrophage infiltration in MEKi-BETi co-treated MPNST PDOX tumors</p>
<p>Heatmap of pair-wise combination matrices obtained by High Throughput Screening</p>
<p>Status of the recurrent MPNST altered genes in 9 MPNSTs cell lines</p>
<div>AbstractPurpose:<p>Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft-tissue sarcoma that develops sporadically or in patients with neurofibromatosis type 1 (NF1). Its development marked by the inactivation of specific suppressor genes (TSG): <i>NF1</i>, <i>CDKN2A</i>, and <i>SUZ12</i>/<i>EED</i> (polycomb repressor complex 2). Each TSG loss can be targeted particular drug inhibitors, we aimed to...
<p>Analyses of the molecular targets triple treatment in vivo NF1-18B MPNST PDOX</p>
<p>Combination Index plots for the 3 selected combos in nine MPNST cell lines</p>
<p>Dosages and administration schedule tested in PDOX models a Maximum Tolerated Dose (MTD) test.</p>
Neurofibromatosis type 1 (NF1) is an autosomal dominant condition in which patients are heterozygous for a disruptive pathogenic variant the NF1 gene. The most characteristic feature of neurofibroma, benign, multi-cellular tumor initiates when cell Schwann lineage gains somatic other allele. Neurofibromas developing at nerve termini skin termed "cutaneous" neurofibromas (cNFs), while those within larger nerves "plexiform." Most develop cNFs beginning late childhood or early adulthood,...
Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas of the nervous system that develop either sporadically or in context neurofibromatosis type 1 (NF1). MPNST diagnosis can be challenging and treatment outcomes poor. We present here a resource consisting genomic characterization 9 widely used human cell lines for their use translational research. NF1-related recapitulated primary copy number profiles, exhibited NF1, CDKN2A, SUZ12/EED tumor suppressor gene (TSG)...
Cutaneous neurofibromas (cNFs) are benign Schwann cell (SC) tumors arising from subepidermal glia. Neurofibromatosis Type 1 (NF1) individuals may develop thousands of cNFs, greatly affecting their quality life. cNF growth is driven by the proliferation NF1(-/-) SCs and interaction with NF1(+/-) microenvironment. We analyzed crosstalk between human cNF-derived fibroblasts (FBs), identifying an expression signature specific to SC-FB interaction. validated secretion proteins involved in immune...
Abstract Background Malignant peripheral nerve sheath tumor (MPNST) constitutes the leading cause of neurofibromatosis type 1–related mortality. MPNSTs contain highly rearranged hyperploid genomes and exhibit a high division rate aggressiveness. We have studied in vitro whether mitotic kinesins KIF11, KIF15, KIF23 functional role maintaining MPNST cell survival can represent potential therapeutic vulnerabilities. Methods expression kinesin mRNAs proteins tumors lines used several assays to...