Biology subjects

Pedron, S.

Publications and source records attributed to Pedron, S..

5 recordsLinked to original sources

bioRxiv2025

Monitoring Whole-Body Inflammation with Gallium-68 Labeled Polydopamine Iron Oxide Particles via Hybrid Immuno-PET-MRI

Monitoring immune reactions via inflammation imaging provides valuable disease prognosis but remains limited by currently available probes and imaging capabilities. In this study, a bimodal imaging probe was developed from microsized polydopamine matrix-based magnetic particles (M3P) functionalized with antibodies that target vascular cell adhesion molecule-1 (VCAM-1) and that are radiolabeled with the radioisotope Gallium-68. This probe combines sensitive inflammation detection via Positron Emission Tomography (immuno-PET) and high-resolution mapping via Magnetic Resonance Imaging (immuno-MRI). The probe represents a powerful disease diagnosis tool to assess the status of systemic inflammation in sepsis as whole-body immuno-PET enables rapid evaluation of the situation, and immuno-MRI provides a more detailed characterization of the identified affected tissues. The elimination profile of the M3P probe is restricted to the mononuclear phagocyte system and does not undergo renal clearance, which is suitable for application in kidney disorders. The efficacy of the hybrid immuno-PET-MRI diagnosis protocol was tested in a murine model of rhabdomyolysis. Kidney inflammation was detected by whole-body immuno-PET, and vascular inflammation patterns could be revealed by high-resolution immuno-MRI. This bimodal PET-MRI probe could significantly improve inflammation monitoring in pathologies characterized by systemic inflammation or lung and kidney dysfunction.

bioengineering↗

bioRxiv2023

ecDNA amplification of MYC drives intratumor copy-number heterogeneity and adaptation to stress in PDAC

Intratumor heterogeneity and phenotypic plasticity drive tumour progression and therapy resistance. Oncogene dosage variation contributes to cell state transitions and phenotypic heterogeneity, thereby providing a substrate for somatic evolution. Nonetheless, the genetic mechanisms underlying phenotypic heterogeneity are still poorly understood. Here, we show that extrachromosomal DNA (ecDNA) is a major source of high-level focal amplification in key oncogenes and a major contributor of MYC heterogeneity in pancreatic ductal adenocarcinoma (PDAC). We demonstrate that ecDNA can drive exceptionally high dosage of MYC and afford cancer cells rapid adaptation to microenvironmental changes. The continued maintenance of extrachromosomal MYC is uniquely ensured by the presence of the selective pressure. We also show that MYC dosage affects cell morphology and dependence of cancer cells on stromal niche factors, with the highest MYC levels correlating with squamous-like phenotypes. Our work provides the first detailed analysis of ecDNAs in PDAC and describes a new genetic mechanism driving MYC heterogeneity in PDAC.

cancer biology↗

bioRxiv2019

Response of neuroglia to hypoxia-induced oxidative stress using enzymatically crosslinked hydrogels

Three-dimensional cultures have exciting potential to mimic aspects of healthy and diseased brain tissue to examine the role of physiological conditions on neural biomarkers as well as disease onset and progression. Hypoxia is associated with oxidative stress, mitochondrial damage, and inflammation, key processes potentially involved in Alzheimers and multiple sclerosis. We describe the use of an enzymatically-crosslinkable gelatin hydrogel system within a microfluidic device to explore the effects of hypoxia-induced oxidative stress on neuroglia, astrocyte reactivity, and myelin production. This versatile platform offers new possibilities for drug discovery and modeling disease progression.

bioengineering↗

bioRxiv2019

Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens

Therapeutic options to treat primary glioblastoma (GBM) tumors are scarce. GBM tumors with epidermal growth factor receptor (EGFR) mutations, in particular a constitutively active EGFRvIII mutant, have extremely poor clinical outcomes. GBM tumors with concurrent EGFR amplification and active phosphatase and tensin homolog (PTEN) are sensitive to the tyrosine kinase inhibitor erlotinib, but the effect is not durable. A persistent challenge to improved treatment is the poorly understood role of cellular, metabolic, and biophysical signals from the GBM tumor microenvironment on therapeutic efficacy and acquired resistance. The intractable nature of studying GBM cell in vivo motivates tissue engineering approaches to replicate aspects of the complex GBM tumor microenvironment. Here, we profile the effect of erlotinib on two patient-derived GBM specimens: EGFR+ GBM12 and EGFRvIII GBM6. We use a three-dimensional gelatin hydrogel to present brain-mimetic hyaluronic acid (HA) and evaluate the coordinated influence of extracellular matrix signals and EGFR mutation status on GBM cell migration, survival and proliferation, as well as signaling pathway activation in response to cyclic erlotinib exposure. Comparable to results observed in vivo for xenograft tumors, erlotinib exposure is not cytotoxic for GBM6 EGFRvIII specimens. We also identify a role of extracellular HA (via CD44) in altering the effect of erlotinib in GBM EGFR+ cells by modifying STAT3 phosphorylation status. Taken together, we report an in vitro tissue engineered platform to monitor signaling associated with poor response to targeted inhibitors in GBM.

bioengineering↗

bioRxiv2018

Influence of hyaluronic acid transitions in tumor microenvironment on glioblastoma malignancy and invasive behavior

The extracellular matrix (ECM) is critical in tumor growth and invasive potential of cancer cells. In glioblastoma tumors, some components of the native brain ECM such as hyaluronic acid (HA) have been suggested as key regulators of processes associated with poor patient outlook such as invasion and therapeutic resistance. Given the importance of cell-mediated remodeling during invasion, it is likely that the molecular weight of available HA polymer may strongly influence GBM progression. Biomaterial platforms therefore provide a unique opportunity to systematically examine the influence of the molecular weight distribution of HA on GBM cell activity. Here we report the relationship between the molecular weight of matrix-bound HA within a methacrylamide-functionalized gelatin (GelMA) hydrogel, the invasive phenotype of a patient-derived xenograft GBM population that exhibits significant in vivo invasivity, and the local production of soluble HA during GBM cell invasion. Hyaluronic acid of different molecular weights spanning a range associated with cell-mediated remodeling (10, 60, and 500 kDa) was photopolymerized into GelMA hydrogels, with cell activity compared to GelMA only conditions (-HA). Polymerization conditions were tuned to create a homologous series of GelMA hydrogels with conserved poroelastic properties (i.e. shear modulus, Poissons ratio, and diffusivity). GBM migration was strongly influenced by HA molecular weight. While markers associated with active remodeling of the HA content, hyaluronan synthase and hyaluronidase, were found to be insensitive to matrix immobilized HA content. These results provide new information regarding the importance of local hyaluronic acid content on the invasive phenotype of GBM.

bioengineering↗